Pub Date : 2025-11-26DOI: 10.1016/j.onano.2025.100272
Manu Sharma, Namita Badoniya
Emerging evidences confirming bromelain’s potential to induce apoptosis and inhibit tumor progression highlights its prospective as adjunctive therapeutic in colorectal cancer malignancies. Despite, high oral doses coupled with poor bioavailability remarkably limits bromelain’s clinical utility, underscoring the necessity of use of innovative delivery strategies. Therefore, the current invention was designed to develop dual pH- and time-responsive bromelain-loaded nanoformulation (Br-PNPs) for controlled and precise delivery to colon with high drug loading capacity and enhanced therapeutic efficacy. pH responsive spherical shaped mucoadhesive nanosized (89.02±6.23 nm) Br-PNPs underscores their potential of minimizing gastric exposure while swelling and mucoadhesivity assured sustained release in colon. Lower IC50 (16.25µg/ml) along with enhanced colon drug concentration attained by Br-PNPs assured their effective colon targeting potential. Br-PNPs significantly reduced disease activity index, tumor burden, aberrant crypt foci and hyperplastic lesions in colon alongside oxidative stress and immunological biomarkers in chemically induced colon cancer model (DMH+DSS) in Wistar rat. The preclinical findings suggested that Br-PNPs have opened up new horizons for establishment of promising contender for colon cancer management in near future.
{"title":"Dual mechanistic approach utilizing pH- and time- responsive bromelain laden polymeric nanoparticles for colon cancer management","authors":"Manu Sharma, Namita Badoniya","doi":"10.1016/j.onano.2025.100272","DOIUrl":"10.1016/j.onano.2025.100272","url":null,"abstract":"<div><div>Emerging evidences confirming bromelain’s potential to induce apoptosis and inhibit tumor progression highlights its prospective as adjunctive therapeutic in colorectal cancer malignancies. Despite, high oral doses coupled with poor bioavailability remarkably limits bromelain’s clinical utility, underscoring the necessity of use of innovative delivery strategies. Therefore, the current invention was designed to develop dual pH- and time-responsive bromelain-loaded nanoformulation (Br-PNPs) for controlled and precise delivery to colon with high drug loading capacity and enhanced therapeutic efficacy. pH responsive spherical shaped mucoadhesive nanosized (89.02±6.23 nm) Br-PNPs underscores their potential of minimizing gastric exposure while swelling and mucoadhesivity assured sustained release in colon. Lower IC<sub>50</sub> (16.25µg/ml) along with enhanced colon drug concentration attained by Br-PNPs assured their effective colon targeting potential. Br-PNPs significantly reduced disease activity index, tumor burden, aberrant crypt foci and hyperplastic lesions in colon alongside oxidative stress and immunological biomarkers in chemically induced colon cancer model (DMH+DSS) in Wistar rat. The preclinical findings suggested that Br-PNPs have opened up new horizons for establishment of promising contender for colon cancer management in near future.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100272"},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-22DOI: 10.1016/j.onano.2025.100269
Mohammed S. Saddik , Basima A.A. Saleem , Ali Khames , Ahmed Adel Alaa-Eldin , Mohamed Ahmed , Hesham.A. Eliwa , Mostafa F. Al-Hakkani , Ahmed M. Ashour , Hamada Hashem , Mohamad A. Ismail , Amany A. Abdel-Rheem
Objective
Colorectal cancer (CRC) therapy with methotrexate (MTX) is limited by toxicity and resistance. This study developed eco-friendly selenium nanoparticles (SeNPs) to enhance MTX delivery and overcome resistance.
Methods
SeNPs were synthesized using a green reduction method and optimized via a Box–Behnken design. Characterization confirmed spherical nanoparticles with an average size of 20–30 nm. MTX loading efficiency (LE%) and release behavior were measured, and biological evaluation was conducted in HCT116 colorectal cancer cells through cytotoxicity, apoptosis (Annexin V/7-AAD), and efflux-transporter assays.
Results
Optimized SeNPs achieved an MTX loading efficiency of ≈48–52 %, with controlled early-phase release. MTX–SeNPs markedly enhanced cytotoxicity, reducing the IC₅₀ to 62.4 µg/mL, compared with 186.6 µg/mL for MTX alone—representing a ∼67 % reduction in required dose. Docking analysis showed selenium interacting with human glutathione reductase, supporting the observed increase in ROS and apoptosis.
Conclusions
Green-synthesized SeNPs significantly improve MTX efficacy by enhancing drug retention, suppressing efflux activity, and reducing resistance. These findings highlight MTX–SeNPs as a promising strategy for CRC treatment and justify further in vivo investigation.
{"title":"Green-synthesized selenium nanoparticles overcoming methotrexate resistance in colorectal cancer","authors":"Mohammed S. Saddik , Basima A.A. Saleem , Ali Khames , Ahmed Adel Alaa-Eldin , Mohamed Ahmed , Hesham.A. Eliwa , Mostafa F. Al-Hakkani , Ahmed M. Ashour , Hamada Hashem , Mohamad A. Ismail , Amany A. Abdel-Rheem","doi":"10.1016/j.onano.2025.100269","DOIUrl":"10.1016/j.onano.2025.100269","url":null,"abstract":"<div><h3>Objective</h3><div>Colorectal cancer (CRC) therapy with methotrexate (MTX) is limited by toxicity and resistance. This study developed eco-friendly selenium nanoparticles (SeNPs) to enhance MTX delivery and overcome resistance.</div></div><div><h3>Methods</h3><div>SeNPs were synthesized using a green reduction method and optimized via a Box–Behnken design. Characterization confirmed spherical nanoparticles with an average size of 20–30 nm. MTX loading efficiency (LE%) and release behavior were measured, and biological evaluation was conducted in HCT116 colorectal cancer cells through cytotoxicity, apoptosis (Annexin V/7-AAD), and efflux-transporter assays.</div></div><div><h3>Results</h3><div>Optimized SeNPs achieved an MTX loading efficiency of ≈48–52 %, with controlled early-phase release. MTX–SeNPs markedly enhanced cytotoxicity, reducing the IC₅₀ to 62.4 µg/mL, compared with 186.6 µg/mL for MTX alone—representing a ∼67 % reduction in required dose. Docking analysis showed selenium interacting with human glutathione reductase, supporting the observed increase in ROS and apoptosis.</div></div><div><h3>Conclusions</h3><div>Green-synthesized SeNPs significantly improve MTX efficacy by enhancing drug retention, suppressing efflux activity, and reducing resistance. These findings highlight MTX–SeNPs as a promising strategy for CRC treatment and justify further in vivo investigation.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-22DOI: 10.1016/j.onano.2025.100271
Nandakumar Selvasudha , Joseph Pushpa Sweety , Gover Antoniraj M , Kandasamy Ruckmani
<div><div>For the past three decades, the principle of nanotechnology has been widely employed to develop pharmaceuticals and bio-pharmaceuticals that are successful for many disease therapies. Several commercially available approved nanomedicines are more efficacious than conventional dosage forms and successfully manage many diseases. The patient's well-being and the certainty to resolve the unresolved challenges of medical science became realistic due to the advent of novel pharmaceutical products based on nanotechnology. These benefits are observed as in humans, the absorption profile of a drug fabricated into nanoparticles varies widely with that of its conventional dosage forms mainly due to the physicochemical modifications and results in highly deviating in-vitro and in-vivo data for the same drug when administered as nanoparticles. The researchers and regulators must frame new guidelines that guide the pharmaceutical industry to develop novel nanomedicines that conform to the desired safety and efficacy. The nanoparticles translational research conducted at the academic level is mainly developing, and the scale-up techniques of the clinically approved nanomedicines are yet to be optimized from the perspective of the manufacturer as well as the regulatory authorities. The IVIVC serves as a reference document that reinforces the pharmaceutical industries to substantiate and expedite the credentials of an oral dosage form about the New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Antibiotic Drug Application (AADA). A poor in-vitro in-vivo correlation (IVIVC) marks a constraint factor, which declines the clinical approval for nanomedicine and its commerce. As on date, neither any specific regulatory guidelines nor any specific calculation methods have been drafted that facilitate the determination of the IVIVC for nanomedicine. Most of the research scientists involved in developing nano/micro/macro formulations do not consider IVIVC an essential criterion. Therefore, a lag in assessing the formulation of assured quality for the next phase happens in the drug development cycle, which terminates the formulation mostly at its pilot scale rather than for its succession as a viable market product. In the pharmaceutical industries, the necessity for IVIVC has been expanded to a greater extent, and a strong IVIVC is recommended to approve the developed nanoformulations of poorly soluble drugs; thus, an appropriate IVIVC model shall be established to expedite the regulatory process for easy and rapid market approval of the developed nanomedicine.</div><div>The objective of the present review includes examining and considering the various associated factors involved in the development of an IVIVC model for nanomedicine, viz., Physico-chemical characteristics and bio-pharmaceutical factors (Formulation and physiological factors); to deliberate on the pros and cons of the various in-vitro dissolution study methods with due consid
{"title":"An overview of the alarming impediments encountered while establishing an apposite IVIVC of nanomedicines necessitated its regulatory approval","authors":"Nandakumar Selvasudha , Joseph Pushpa Sweety , Gover Antoniraj M , Kandasamy Ruckmani","doi":"10.1016/j.onano.2025.100271","DOIUrl":"10.1016/j.onano.2025.100271","url":null,"abstract":"<div><div>For the past three decades, the principle of nanotechnology has been widely employed to develop pharmaceuticals and bio-pharmaceuticals that are successful for many disease therapies. Several commercially available approved nanomedicines are more efficacious than conventional dosage forms and successfully manage many diseases. The patient's well-being and the certainty to resolve the unresolved challenges of medical science became realistic due to the advent of novel pharmaceutical products based on nanotechnology. These benefits are observed as in humans, the absorption profile of a drug fabricated into nanoparticles varies widely with that of its conventional dosage forms mainly due to the physicochemical modifications and results in highly deviating in-vitro and in-vivo data for the same drug when administered as nanoparticles. The researchers and regulators must frame new guidelines that guide the pharmaceutical industry to develop novel nanomedicines that conform to the desired safety and efficacy. The nanoparticles translational research conducted at the academic level is mainly developing, and the scale-up techniques of the clinically approved nanomedicines are yet to be optimized from the perspective of the manufacturer as well as the regulatory authorities. The IVIVC serves as a reference document that reinforces the pharmaceutical industries to substantiate and expedite the credentials of an oral dosage form about the New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Antibiotic Drug Application (AADA). A poor in-vitro in-vivo correlation (IVIVC) marks a constraint factor, which declines the clinical approval for nanomedicine and its commerce. As on date, neither any specific regulatory guidelines nor any specific calculation methods have been drafted that facilitate the determination of the IVIVC for nanomedicine. Most of the research scientists involved in developing nano/micro/macro formulations do not consider IVIVC an essential criterion. Therefore, a lag in assessing the formulation of assured quality for the next phase happens in the drug development cycle, which terminates the formulation mostly at its pilot scale rather than for its succession as a viable market product. In the pharmaceutical industries, the necessity for IVIVC has been expanded to a greater extent, and a strong IVIVC is recommended to approve the developed nanoformulations of poorly soluble drugs; thus, an appropriate IVIVC model shall be established to expedite the regulatory process for easy and rapid market approval of the developed nanomedicine.</div><div>The objective of the present review includes examining and considering the various associated factors involved in the development of an IVIVC model for nanomedicine, viz., Physico-chemical characteristics and bio-pharmaceutical factors (Formulation and physiological factors); to deliberate on the pros and cons of the various in-vitro dissolution study methods with due consid","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-20DOI: 10.1016/j.onano.2025.100270
Salam Shanta Taher, Khalid K. Al-Kinani
Effective delivery of antiretroviral drugs to the brain is a major hurdle in treating central nervous system (CNS) HIV infections. This study developed an intranasal in situ gel containing dolutegravir sodium-loaded nanostructured lipid carriers (DTGs-NLCs) for targeted nose-to-brain delivery. DTGs-NLCs were prepared using a modified melt emulsification-ultrasonication method, yielding nanocarriers with a size of 80.8 ± 10.4 nm, zeta potential of –13±1.4 mV, and entrapment efficiency of 80.7 ± 0.48 %. These NLCs were incorporated into a thermosensitive in situ gel matrix composed of poloxamer 407 and carbopol 934P. The in vitro drug release from the gel was significantly enhanced compared to the free drug (p < 0.05). Rheological studies confirmed the formulation’s non-Newtonian behavior, good spreadability (5.9 ± 0.13 cm), and strong mucoadhesiveness (1116.86 ± 20 dyne/cm²). Safety evaluations demonstrated excellent hemocompatibility and biocompatibility. Pharmacokinetic studies revealed that intranasal administration achieved higher brain concentrations (Cmax: 35.4 ± 3.6 µg/g; AUC₀–₄₈: 193.22±14.66 µg·h/g) and faster absorption (Tmax: 1 h) than intravenous delivery. These results indicate that the DTGs-NLC in situ gel offers a safe, non-invasive, and efficient approach for enhanced brain targeting, showing great promise for treating CNS complications of HIV, including neuroAIDS.
{"title":"Formulation and characterization of dolutegravir sodium-loaded nanostructured lipid carrier in situ gel for targeted brain delivery via intranasal route","authors":"Salam Shanta Taher, Khalid K. Al-Kinani","doi":"10.1016/j.onano.2025.100270","DOIUrl":"10.1016/j.onano.2025.100270","url":null,"abstract":"<div><div>Effective delivery of antiretroviral drugs to the brain is a major hurdle in treating central nervous system (CNS) HIV infections. This study developed an intranasal in situ gel containing dolutegravir sodium-loaded nanostructured lipid carriers (DTGs-NLCs) for targeted nose-to-brain delivery. DTGs-NLCs were prepared using a modified melt emulsification-ultrasonication method, yielding nanocarriers with a size of 80.8 ± 10.4 nm, zeta potential of –13±1.4 mV, and entrapment efficiency of 80.7 ± 0.48 %. These NLCs were incorporated into a thermosensitive in situ gel matrix composed of poloxamer 407 and carbopol 934P. The in vitro drug release from the gel was significantly enhanced compared to the free drug (<em>p</em> < 0.05). Rheological studies confirmed the formulation’s non-Newtonian behavior, good spreadability (5.9 ± 0.13 cm), and strong mucoadhesiveness (1116.86 ± 20 dyne/cm²). Safety evaluations demonstrated excellent hemocompatibility and biocompatibility. Pharmacokinetic studies revealed that intranasal administration achieved higher brain concentrations (C<sub>max</sub>: 35.4 ± 3.6 µg/g; AUC₀–₄₈: 193.22±14.66 µg·h/g) and faster absorption (T<sub>max</sub>: 1 h) than intravenous delivery. These results indicate that the DTGs-NLC in situ gel offers a safe, non-invasive, and efficient approach for enhanced brain targeting, showing great promise for treating CNS complications of HIV, including neuroAIDS.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study presents the development and characterization of a novel niosome delivery system incorporating whole tomato extract for topical application. The formulation was optimized using a Box–Behnken design (BBD) by response surface methodology (RSM) to achieve high entrapment efficiency, small vesicle size, and low polydispersity index (PDI). The optimal formulation (2 mM Span 60, 1 mM cholesterol, 1 % extract) yielded an entrapment efficiency of 90.34 %, particle size of 222.06 nm, and PDI of 0.34. Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses confirmed successful encapsulation and nanoscale spherical morphology. In vitro release studies demonstrated distinct kinetic behaviors: the whole extract followed Higuchi model, while lycopene exhibited zero-order model. The optimized tomato extract–loaded niosomes (TNS) exhibited enhanced stability and demonstrated significant biological activity, including ultraviolet ̶ B (UVB) protection in immortalized human keratinocyte cell lines (HaCaT) and anti-melanogenic effects in murine melanoma cell lines (B16F10). Notably, tomato extract–loaded niosomes (TNS) significantly downregulated the expression of melanogenesis-related proteins, microphthalmia-associated transcription factor (MITF) and tyrosinase, as confirmed by Western blot analysis. These findings support the potential use of tomato extract-loaded niosomes (TNS) as multifunctional cosmetic ingredients for photoprotection and skin whitening applications.
{"title":"Response surface methodology - optimized niosomes encapsulating whole tomato extract: Release profile and mechanistic insights for UVB protection and anti-melanogenesis applications","authors":"Nattawadee Kanpipit , Sakornchon Mattariganont , Likit Temprom , Prutchayawoot Thopan , Khomsorn Lomthaisong , Sriprajak Krongsuk , Suthasinee Thapphasaraphong","doi":"10.1016/j.onano.2025.100267","DOIUrl":"10.1016/j.onano.2025.100267","url":null,"abstract":"<div><div>This study presents the development and characterization of a novel niosome delivery system incorporating whole tomato extract for topical application. The formulation was optimized using a Box–Behnken design (BBD) by response surface methodology (RSM) to achieve high entrapment efficiency, small vesicle size, and low polydispersity index (PDI). The optimal formulation (2 mM Span 60, 1 mM cholesterol, 1 % extract) yielded an entrapment efficiency of 90.34 %, particle size of 222.06 nm, and PDI of 0.34. Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses confirmed successful encapsulation and nanoscale spherical morphology. In vitro release studies demonstrated distinct kinetic behaviors: the whole extract followed Higuchi model, while lycopene exhibited zero-order model. The optimized tomato extract–loaded niosomes (TNS) exhibited enhanced stability and demonstrated significant biological activity, including ultraviolet ̶ B (UVB) protection in immortalized human keratinocyte cell lines (HaCaT) and anti-melanogenic effects in murine melanoma cell lines (B16F10). Notably, tomato extract–loaded niosomes (TNS) significantly downregulated the expression of melanogenesis-related proteins, microphthalmia-associated transcription factor (MITF) and tyrosinase, as confirmed by Western blot analysis. These findings support the potential use of tomato extract-loaded niosomes (TNS) as multifunctional cosmetic ingredients for photoprotection and skin whitening applications.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.onano.2025.100266
Sruti Murali , Jayamani Thomas , John Abraham , Vignesh Kanna , Sivaramakrishnan Ramachandiran , Suruthi SS
Background
Nanotechnology is reshaping the biomedical landscape by offering unprecedented capabilities in disease diagnostics, targeted therapy, and biosensing. Nanoparticles (NPs), owing to their unique physicochemical properties, enable ultra-sensitive biomarker detection, real-time monitoring, and minimally invasive assays across oncology, infectious diseases, and neurology. However, their biological interactions also raise significant concerns regarding organ-specific toxicity, particularly in metabolic systems.
Objective
This systematic review and meta-analysis aim to integrate current evidence on nanoparticle-based diagnostic applications with emerging insights into their toxicological impacts on key metabolic organs — liver, kidney, pancreas, spleen, and adipose tissue. It further examines mechanistic pathways, dose-dependent effects, and translational challenges to bridge the gap between innovation and biosafety.
Methods
A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar from January 2015 to October 2025 following PRISMA 2020 guidelines. Eligible studies reported quantitative diagnostic performance metrics (e.g., limit of detection, sensitivity, multiplexing capacity) or biological outcomes (e.g., oxidative stress, apoptosis, fibrosis, endocrine disruption) related to NP exposure. Meta-analytic synthesis was performed on 42 studies reporting comparable quantitative toxicity data.
Results
Diagnostic applications of metallic, polymeric, photonic, and hybrid nanoparticles demonstrated up to a 1000-fold improvement in sensitivity over conventional assays, with mean detection limits reaching the femtomolar range. However, pooled toxicity analysis revealed significant organ-specific risks: hepatic ROS generation (standardized mean difference [SMD] = 1.42, 95 % CI: 1.10–1.75), renal tubular apoptosis (SMD = 1.27, 95 % CI: 0.94–1.61), and β-cell impairment (SMD = 1.18, 95 % CI: 0.88–1.49). Translational challenges remain due to poor clearance kinetics, chronic inflammation, and incomplete regulatory frameworks.
Conclusion
Nanoparticles hold transformative potential in precision diagnostics, but their clinical adoption demands a nuanced understanding of toxicological trade-offs. Future research must focus on biodegradable and renal-clearable materials, mechanistically guided design strategies, standardized toxicological protocols, and AI-driven predictive models. This review provides a dual-perspective framework that integrates diagnostic breakthroughs with biosafety imperatives, guiding the next phase of nanomedicine toward safe and effective clinical translation.
{"title":"Nanodiagnostics and nanotoxicology: A systematic review and meta-analysis on nanoparticle applications and safety in metabolic organs","authors":"Sruti Murali , Jayamani Thomas , John Abraham , Vignesh Kanna , Sivaramakrishnan Ramachandiran , Suruthi SS","doi":"10.1016/j.onano.2025.100266","DOIUrl":"10.1016/j.onano.2025.100266","url":null,"abstract":"<div><h3>Background</h3><div>Nanotechnology is reshaping the biomedical landscape by offering unprecedented capabilities in disease diagnostics, targeted therapy, and biosensing. Nanoparticles (NPs), owing to their unique physicochemical properties, enable ultra-sensitive biomarker detection, real-time monitoring, and minimally invasive assays across oncology, infectious diseases, and neurology. However, their biological interactions also raise significant concerns regarding organ-specific toxicity, particularly in metabolic systems.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aim to integrate current evidence on nanoparticle-based diagnostic applications with emerging insights into their toxicological impacts on key metabolic organs — liver, kidney, pancreas, spleen, and adipose tissue. It further examines mechanistic pathways, dose-dependent effects, and translational challenges to bridge the gap between innovation and biosafety.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar from January 2015 to October 2025 following PRISMA 2020 guidelines. Eligible studies reported quantitative diagnostic performance metrics (e.g., limit of detection, sensitivity, multiplexing capacity) or biological outcomes (e.g., oxidative stress, apoptosis, fibrosis, endocrine disruption) related to NP exposure. Meta-analytic synthesis was performed on 42 studies reporting comparable quantitative toxicity data.</div></div><div><h3>Results</h3><div>Diagnostic applications of metallic, polymeric, photonic, and hybrid nanoparticles demonstrated up to a 1000-fold improvement in sensitivity over conventional assays, with mean detection limits reaching the femtomolar range. However, pooled toxicity analysis revealed significant organ-specific risks: hepatic ROS generation (standardized mean difference [SMD] = 1.42, 95 % CI: 1.10–1.75), renal tubular apoptosis (SMD = 1.27, 95 % CI: 0.94–1.61), and β-cell impairment (SMD = 1.18, 95 % CI: 0.88–1.49). Translational challenges remain due to poor clearance kinetics, chronic inflammation, and incomplete regulatory frameworks.</div></div><div><h3>Conclusion</h3><div>Nanoparticles hold transformative potential in precision diagnostics, but their clinical adoption demands a nuanced understanding of toxicological trade-offs. Future research must focus on biodegradable and renal-clearable materials, mechanistically guided design strategies, standardized toxicological protocols, and AI-driven predictive models. This review provides a dual-perspective framework that integrates diagnostic breakthroughs with biosafety imperatives, guiding the next phase of nanomedicine toward safe and effective clinical translation.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.onano.2025.100265
Mahmood A. Haiss, Shaimaa N. Abd Alhammid
The swiftly changing technological and regulatory environments in the development of pharmaceutical drugs require risk based approach that integrates multivariate analysis utilizing Quality by Design (QbD). Flunarizine, a poorly water-soluble calcium channel blocker utilized for migraine treatment, exhibits low bioavailability. Spanlastics, contemporary nonionic based surfactant nanovesicles, enhance medication penetration due to their fluidic nature. Consequently, we optimized flunarizine spanlastic nanovesicles (FNZ-SNVs) utilizing formulation by design principles and investigated the viability of nose-to-brain delivery for migraine management. Ishikawa diagram was utilized to identify the risk factors that may affect the critical quality attributes of FNZ-SNVs. The use of Plackett–Burman experimental design was employed to test eight distinct formula and process factors affecting vesicle size, zeta potential, vesicle deformability, and encapsulation efficiency. Utilizing Pareto charts, three critical parameters were identified: type of vesicle builder (Span 60), type of EA (Tween 60), and sonication duration. Three levels of these essential factors were tuned by formulation by design to minimize vesicle size and enhance encapsulation efficiency, and vesicle deformability of FNZ-SNVs. The optimized FNZ-SNVs exhibited a vesicle size of 95.5 nm, an encapsulation efficiency of 86%, a relative deformability of 4.8 minutes, and a dissolving efficiency of 90.2%. Consequently, the optimized formula was integrated into an insitu-gel (IG) and investigated for additional in vivo assessment, which demonstrated that the degree of FNZ-SIG intranasal delivered to the brain was significantly greater than that of the intravenous FNZ solution, exhibiting an exceptionally elevated drug targeting index (DTI) of 1.12 and (DTE%) 112.1. This study illustrates the successful implementation of risk management and Quality by Design (QbD) methodologies in the formulation of brain-targeting release of FNZ-SIGs.
{"title":"Quality by design of ultra deformable nanovesicles loaded with flunarizine for brain targeting utilizing risk assessment and multivariate analytical methods","authors":"Mahmood A. Haiss, Shaimaa N. Abd Alhammid","doi":"10.1016/j.onano.2025.100265","DOIUrl":"10.1016/j.onano.2025.100265","url":null,"abstract":"<div><div>The swiftly changing technological and regulatory environments in the development of pharmaceutical drugs require risk based approach that integrates multivariate analysis utilizing Quality by Design (QbD). Flunarizine, a poorly water-soluble calcium channel blocker utilized for migraine treatment, exhibits low bioavailability. Spanlastics, contemporary nonionic based surfactant nanovesicles, enhance medication penetration due to their fluidic nature. Consequently, we optimized flunarizine spanlastic nanovesicles (FNZ-SNVs) utilizing formulation by design principles and investigated the viability of nose-to-brain delivery for migraine management. Ishikawa diagram was utilized to identify the risk factors that may affect the critical quality attributes of FNZ-SNVs. The use of Plackett–Burman experimental design was employed to test eight distinct formula and process factors affecting vesicle size, zeta potential, vesicle deformability, and encapsulation efficiency. Utilizing Pareto charts, three critical parameters were identified: type of vesicle builder (Span 60), type of EA (Tween 60), and sonication duration. Three levels of these essential factors were tuned by formulation by design to minimize vesicle size and enhance encapsulation efficiency, and vesicle deformability of FNZ-SNVs. The optimized FNZ-SNVs exhibited a vesicle size of 95.5 nm, an encapsulation efficiency of 86%, a relative deformability of 4.8 minutes, and a dissolving efficiency of 90.2%. Consequently, the optimized formula was integrated into an insitu-gel (IG) and investigated for additional in vivo assessment, which demonstrated that the degree of FNZ-SIG intranasal delivered to the brain was significantly greater than that of the intravenous FNZ solution, exhibiting an exceptionally elevated drug targeting index (DTI) of 1.12 and (DTE%) 112.1. This study illustrates the successful implementation of risk management and Quality by Design (QbD) methodologies in the formulation of brain-targeting release of FNZ-SIGs.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145580037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.onano.2025.100264
Dina Mohamed Mahmoud , Mohamed Mahmoud Abdelfatah , Tamer Mohamed Mahmoud , Omiya Ali Hasan , Randa Mohammed Zaki , Obaid Afzal , Mostafa Asim Darwish , Mohamed G. Ewees , Mostafa Nasr Taha , Mahmoud Mohamed Omar
Infected wounds pose a significant clinical challenge, driving the need for advanced dressings that actively combat infection and promote healing. This study developed a novel bio-composite film by integrating silver nanoparticle-enhanced, metronidazole-loaded lipidic nanovesicles into a snail slime collagen-chitosan matrix. A Design of Experiment optimized lipidic nanovesicle formulation (loaded with metronidazole) (Lop) was fabricated and characterized (DLS, drug release). Silver nanoparticles (AgNPs) were incorporated to form optimized nanovesicle formulation incorporating Silver Nanoparticles (Lop-AgNPs), which were embedded into a snail slime collagen (SSC)-chitosan (CS) matrix to create the final Lop.M film (optimized bio-composite film (Lop-AgNPs in a Snail Slime Collagen-Chitosan matrix). The film was tested for physicochemical properties, antimicrobial activity (disc diffusion), and efficacy in a rat wound model. The optimized formulation (Lop) showed a vesicle size of 339.5±3.1 nm, zeta potential of -58.2 ± 2.8 mV, and entrapment efficiency of 88.6 ± 4.5% w/w, with 45.9 ± 3.2% w/w cumulative metronidazole release after 4 h. Upon silver incorporation, vesicle size increased to 358.9 ± 5.7 nm and zeta potential to -62.1±3.2 mV. The composite film (Lop.M) exhibited a swelling index (SI) of 18.2 ± 0.4% w/w, film thickness of 0.71 ± 0.05 mm, and folding endurance > 50 folds. Antimicrobial zones of inhibition reached 50 mm for P. aeruginosa and 45 mm for Escherichia coli. In vivo, Lop.M-treated wounds demonstrated 96.4 ± 2.3% closure by day 14 compared to 68.1 ± 3.8% in controls. The Lop.M film, which demonstrated 96.4% wound closure in 14 days and potent antimicrobial activity, presents a strategy for wound management that combines robust antimicrobial action with active promotion of tissue regeneration.
{"title":"Snail-collagen/chitosan nanocomposite film with silver nanoparticles for antimicrobial and regenerative wound healing","authors":"Dina Mohamed Mahmoud , Mohamed Mahmoud Abdelfatah , Tamer Mohamed Mahmoud , Omiya Ali Hasan , Randa Mohammed Zaki , Obaid Afzal , Mostafa Asim Darwish , Mohamed G. Ewees , Mostafa Nasr Taha , Mahmoud Mohamed Omar","doi":"10.1016/j.onano.2025.100264","DOIUrl":"10.1016/j.onano.2025.100264","url":null,"abstract":"<div><div>Infected wounds pose a significant clinical challenge, driving the need for advanced dressings that actively combat infection and promote healing. This study developed a novel bio-composite film by integrating silver nanoparticle-enhanced, metronidazole-loaded lipidic nanovesicles into a snail slime collagen-chitosan matrix. A Design of Experiment optimized lipidic nanovesicle formulation (loaded with metronidazole) (Lop) was fabricated and characterized (DLS, drug release). Silver nanoparticles (AgNPs) were incorporated to form optimized nanovesicle formulation incorporating Silver Nanoparticles (Lop-AgNPs), which were embedded into a snail slime collagen (SSC)-chitosan (CS) matrix to create the final Lop.M film (optimized bio-composite film (Lop-AgNPs in a Snail Slime Collagen-Chitosan matrix). The film was tested for physicochemical properties, antimicrobial activity (disc diffusion), and efficacy in a rat wound model. The optimized formulation (Lop) showed a vesicle size of <strong>339.5</strong> <strong>±</strong> <strong>3.1</strong> nm, zeta potential of -58.2 ± 2.8 mV, and entrapment efficiency of 88.6 ± 4.5% w/w, with 45.9 ± 3.2% w/w cumulative metronidazole release after 4 h. Upon silver incorporation, vesicle size increased to 358.9 ± 5.7 nm and zeta potential to <strong>-62.1</strong> <strong>±</strong> <strong>3.2</strong> mV. The composite film (Lop.M) exhibited a swelling index (SI) of 18.2 ± 0.4% w/w, film thickness of 0.71 ± 0.05 mm, and folding endurance > 50 folds. Antimicrobial zones of inhibition reached 50 mm for <em>P. aeruginosa</em> and 45 mm for <em>Escherichia coli. In vivo</em>, Lop.M-treated wounds demonstrated 96.4 ± 2.3% closure by day 14 compared to 68.1 ± 3.8% in controls. The Lop.M film, which demonstrated 96.4% wound closure in 14 days and potent antimicrobial activity, presents a strategy for wound management that combines robust antimicrobial action with active promotion of tissue regeneration.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"27 ","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.onano.2025.100263
Tubagus Akmal , Yedi Herdiana , Ahmed Fouad Abdelwahab Mohammed , Safwat A. Mahmoud , Khaled M. Elamin , Gofarana Wilar , Nasrul Wathoni
Chitosan-functionalized selenium nanoparticles (CS-SeNPs) integrate selenium’s redox-active anticancer potential with chitosan’s stabilization, mucoadhesion, and ligand-ready surface to enable tumor-selective delivery. This review consolidates advances in chemical, physical, and green syntheses; relates processing to size, charge, colloidal stability, and drug loading; and maps these attributes to biodistribution, cellular uptake, and controlled release. Emphasis is placed on modified chitosan derivatives that confer pH or redox responsiveness, enhanced permeability and retention, active targeting, and co-delivery of chemotherapeutics or photosensitizers. Anticancer mechanisms encompass mitochondrial apoptosis, ROS modulation, cell-cycle arrest, anti-metastatic activity, and chemo- or photo-synergy. A critical comparison with metal-oxide platforms and discussion of environmental fate, biofilm reactor data, hemocompatibility, and immunotoxicity delineate benefits and remaining risks. Key translational priorities include scalable green synthesis, robust physicochemical and release specifications, in vivo exposure–response models, and regulatory-grade safety packages. CS-SeNPs thus represent a credible path toward precision oncology.
{"title":"Chitosan-functionalized selenium nanoparticles for targeted cancer therapy: Advances in synthesis, stability, and tumor-specific delivery","authors":"Tubagus Akmal , Yedi Herdiana , Ahmed Fouad Abdelwahab Mohammed , Safwat A. Mahmoud , Khaled M. Elamin , Gofarana Wilar , Nasrul Wathoni","doi":"10.1016/j.onano.2025.100263","DOIUrl":"10.1016/j.onano.2025.100263","url":null,"abstract":"<div><div>Chitosan-functionalized selenium nanoparticles (CS-SeNPs) integrate selenium’s redox-active anticancer potential with chitosan’s stabilization, mucoadhesion, and ligand-ready surface to enable tumor-selective delivery. This review consolidates advances in chemical, physical, and green syntheses; relates processing to size, charge, colloidal stability, and drug loading; and maps these attributes to biodistribution, cellular uptake, and controlled release. Emphasis is placed on modified chitosan derivatives that confer pH or redox responsiveness, enhanced permeability and retention, active targeting, and co-delivery of chemotherapeutics or photosensitizers. Anticancer mechanisms encompass mitochondrial apoptosis, ROS modulation, cell-cycle arrest, anti-metastatic activity, and chemo- or photo-synergy. A critical comparison with metal-oxide platforms and discussion of environmental fate, biofilm reactor data, hemocompatibility, and immunotoxicity delineate benefits and remaining risks. Key translational priorities include scalable green synthesis, robust physicochemical and release specifications, in vivo exposure–response models, and regulatory-grade safety packages. CS-SeNPs thus represent a credible path toward precision oncology.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"26 ","pages":"Article 100263"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1016/j.onano.2025.100262
Thi Thanh Huong Le , Van Hung Hoang , Thi Quynh Nguyen , Dac Trung Nguyen , Viet Hoang , Thu Huong Trinh , Thi Tam Khieu , Phu Hung Nguyen
Plant-based green nanotechnology provides a promising strategy that integrates phytochemicals with metallic nanoparticles for targeted cancer therapy. In this study, silver nanoparticles (Eml-AgNPs) synthesized using Embelia laeta (L.) Mez. leaf extract were investigated for their anticancer potential. The Eml-AgNPs were spherical, crystalline, and averaged 13.4 ± 4.6 nm in size, as confirmed by UV–Vis spectroscopy (absorption peak at 453 nm), XRD, FTIR, and TEM analyses. UPLC-QToF-MS profiling revealed 13 bioactive molecules bound to the nanoparticle surface, contributing to their stability and anticancer efficacy. Eml-AgNPs demonstrated potent, concentration-dependent cytotoxicity against HepG2, AGS, MCF-7, and MKN45 cancer cell lines, with IC₅₀ values ranging from 0.78 µg/mL to 1.67 µg/mL. In 3D tumorsphere cultures, treatment with Eml-AgNPs (2–5 µg/mL) significantly disrupted spheroid morphology and cellular cohesion. Mechanistic studies indicated ROS-mediated apoptosis, evidenced by a 36.7 % increase in Annexin V-FITC-positive cells (p < 0.01) and a 32.7 % elevation in ROS generation following treatment with 5 µg/mL Eml-AgNPs (p < 0.01). Furthermore, expression of pro-apoptotic genes including CASP8, CASP9, GADD45, and BAX was significantly upregulated. Collectively, these findings highlight the potential of Eml-AgNPs as a green nanotherapeutic platform, leveraging phytochemical synergy to induce oxidative stress-driven apoptosis in cancer cells. Further in vivo studies are needed to confirm the efficacy and safety of Eml-AgNPs for potential biomedical applications.
{"title":"Phytochemical-capped silver nanoparticles from the medicinal plant Embelia laeta disrupting 3D tumorspheres and inducing ROS-mediated apoptosis in MCF-7 breast cancer cells","authors":"Thi Thanh Huong Le , Van Hung Hoang , Thi Quynh Nguyen , Dac Trung Nguyen , Viet Hoang , Thu Huong Trinh , Thi Tam Khieu , Phu Hung Nguyen","doi":"10.1016/j.onano.2025.100262","DOIUrl":"10.1016/j.onano.2025.100262","url":null,"abstract":"<div><div>Plant-based green nanotechnology provides a promising strategy that integrates phytochemicals with metallic nanoparticles for targeted cancer therapy. In this study, silver nanoparticles (Eml-AgNPs) synthesized using <em>Embelia laeta</em> (L.) Mez. leaf extract were investigated for their anticancer potential. The Eml-AgNPs were spherical, crystalline, and averaged 13.4 ± 4.6 nm in size, as confirmed by UV–Vis spectroscopy (absorption peak at 453 nm), XRD, FTIR, and TEM analyses. UPLC-QToF-MS profiling revealed 13 bioactive molecules bound to the nanoparticle surface, contributing to their stability and anticancer efficacy. Eml-AgNPs demonstrated potent, concentration-dependent cytotoxicity against HepG2, AGS, MCF-7, and MKN45 cancer cell lines, with IC₅₀ values ranging from 0.78 µg/mL to 1.67 µg/mL. In 3D tumorsphere cultures, treatment with Eml-AgNPs (2–5 µg/mL) significantly disrupted spheroid morphology and cellular cohesion. Mechanistic studies indicated ROS-mediated apoptosis, evidenced by a 36.7 % increase in Annexin V-FITC-positive cells (<em>p</em> < 0.01) and a 32.7 % elevation in ROS generation following treatment with 5 µg/mL Eml-AgNPs (<em>p</em> < 0.01). Furthermore, expression of pro-apoptotic genes including <em>CASP8, CASP9, GADD45</em>, and <em>BAX</em> was significantly upregulated. Collectively, these findings highlight the potential of Eml-AgNPs as a green nanotherapeutic platform, leveraging phytochemical synergy to induce oxidative stress-driven apoptosis in cancer cells. Further in vivo studies are needed to confirm the efficacy and safety of Eml-AgNPs for potential biomedical applications.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"26 ","pages":"Article 100262"},"PeriodicalIF":0.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}