Pub Date : 2022-12-01DOI: 10.1080/10717544.2021.2023696
Akula S N Murthy, Sanket Das, Tejinder Singh, Tae-Wan Kim, Nasim Sepay, Seob Jeon, Jungkyun Im
As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.
{"title":"Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex.","authors":"Akula S N Murthy, Sanket Das, Tejinder Singh, Tae-Wan Kim, Nasim Sepay, Seob Jeon, Jungkyun Im","doi":"10.1080/10717544.2021.2023696","DOIUrl":"https://doi.org/10.1080/10717544.2021.2023696","url":null,"abstract":"<p><p>As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39671801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/10717544.2022.2053762
Qi-Rui Li, Hua-Zhen Xu, Rong-Cheng Xiao, Yan Liu, Jun-Ming Tang, Jian Li, Ting-Ting Yu, Bin Liu, Liu-Gen Li, Mei-Fang Wang, Ning Han, Yong-Hong Xu, Chao Wang, Naoki Komatsu, Li Zhao, Xing-Chun Peng, Tong-Fei Li, Xiao Chen
The present work aims to prove the concept of tumor-targeted drug delivery mediated by platelets. Doxorubicin (DOX) attached to nanodiamonds (ND-DOX) was investigated as the model payload drug of platelets. In vitro experiments first showed that ND-DOX could be loaded in mouse platelets in a dose-dependent manner with a markedly higher efficiency and capacity than free DOX. ND-DOX-loaded platelets (Plt@ND-DOX) maintained viability and ND-DOX could be stably held in the platelets for at least 4 hr. Next, mouse Lewis lung cancer cells were found to activate Plt@ND-DOX and thereby stimulate cargo unloading of Plt@ND-DOX. The unloaded ND-DOX was taken up by co-cultured cancer cells which consequently exhibited loss of viability, proliferation suppression and apoptosis. In vivo, Plt@ND-DOX displayed significantly prolonged blood circulation time over ND-DOX and DOX in mice, and Lewis tumor grafts demonstrated infiltration, activation and cargo unloading of Plt@ND-DOX in the tumor tissue. Consequently, Plt@ND-DOX effectively reversed the growth of Lewis tumor grafts which exhibited significant inhibition of cell proliferation and apoptosis. Importantly, Plt@ND-DOX displayed a markedly higher therapeutic potency than free DOX but without the severe systemic toxicity associated with DOX. Our findings are concrete proof of platelets as efficient and efficacious carriers for tumor-targeted nano-drug delivery with the following features: 1) large loading capacity and high loading efficiency, 2) good tolerance of cargo drug, 3) stable cargo retention and no cargo unloading in the absence of stimulation, 4) prolonged blood circulation time, and 5) excellent tumor distribution and tumor-activated drug unloading leading to high therapeutic potency and few adverse effects. Platelets hold great potential as efficient and efficacious carriers for tumor-targeted nano-drug delivery.
{"title":"Platelets are highly efficient and efficacious carriers for tumor-targeted nano-drug delivery.","authors":"Qi-Rui Li, Hua-Zhen Xu, Rong-Cheng Xiao, Yan Liu, Jun-Ming Tang, Jian Li, Ting-Ting Yu, Bin Liu, Liu-Gen Li, Mei-Fang Wang, Ning Han, Yong-Hong Xu, Chao Wang, Naoki Komatsu, Li Zhao, Xing-Chun Peng, Tong-Fei Li, Xiao Chen","doi":"10.1080/10717544.2022.2053762","DOIUrl":"https://doi.org/10.1080/10717544.2022.2053762","url":null,"abstract":"<p><p>The present work aims to prove the concept of tumor-targeted drug delivery mediated by platelets. Doxorubicin (DOX) attached to nanodiamonds (ND-DOX) was investigated as the model payload drug of platelets. In vitro experiments first showed that ND-DOX could be loaded in mouse platelets in a dose-dependent manner with a markedly higher efficiency and capacity than free DOX. ND-DOX-loaded platelets (Plt@ND-DOX) maintained viability and ND-DOX could be stably held in the platelets for at least 4 hr. Next, mouse Lewis lung cancer cells were found to activate Plt@ND-DOX and thereby stimulate cargo unloading of Plt@ND-DOX. The unloaded ND-DOX was taken up by co-cultured cancer cells which consequently exhibited loss of viability, proliferation suppression and apoptosis. In vivo, Plt@ND-DOX displayed significantly prolonged blood circulation time over ND-DOX and DOX in mice, and Lewis tumor grafts demonstrated infiltration, activation and cargo unloading of Plt@ND-DOX in the tumor tissue. Consequently, Plt@ND-DOX effectively reversed the growth of Lewis tumor grafts which exhibited significant inhibition of cell proliferation and apoptosis. Importantly, Plt@ND-DOX displayed a markedly higher therapeutic potency than free DOX but without the severe systemic toxicity associated with DOX. Our findings are concrete proof of platelets as efficient and efficacious carriers for tumor-targeted nano-drug delivery with the following features: 1) large loading capacity and high loading efficiency, 2) good tolerance of cargo drug, 3) stable cargo retention and no cargo unloading in the absence of stimulation, 4) prolonged blood circulation time, and 5) excellent tumor distribution and tumor-activated drug unloading leading to high therapeutic potency and few adverse effects. Platelets hold great potential as efficient and efficacious carriers for tumor-targeted nano-drug delivery.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40313513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/10717544.2022.2108939
Rofida Albash, Rania Moataz El-Dahmy, Mohammed I A Hamed, Khaled M Darwish, Abdulrahman M Alahdal, Amira B Kassem, Abdurrahman M Fahmy
Abstract Levocetirizine hydrochloride (LVC) is an antihistaminic drug that is repurposed for the treatment of alopecia. This investigation is targeted for formulating LVC into cationic ceramide/phospholipid composite (CCPCs) for the management of alopecia. CCPCs were fabricated by ethanol-injection approach, through a central composite experiment. CCPCs were evaluated by inspecting their entrapment efficiency (EE%), polydispersity index (PDI), particle size (PS), and zeta potential (ZP). The optimum CCPCs were additionally studied by in-vitro, ex-vivo, in-silico, and in-vivo studies. The fabricated CCPCs had acceptable EE%, PS, PDI, and ZP values. The statistical optimization elected optimum CCPCs composed of 5 mg hyaluronic acid, 10 mg ceramide III, and 5 mg dimethyldidodecylammonium bromide employing phytantriol as a permeation enhancer. The optimum CCPCs had EE%, PS, PDI, and ZP of 88.36 ± 0.34%, 479.00 ± 50.34 nm, 0.377 ± 0.0035, and 20.20 ± 1.13 mV, respectively. The optimum CCPC maintained its stability for up to 90 days. It also viewed vesicles of tube shape via transmission electron microscope. The in-silico assessment resulted in better interaction and stability between LVC and vesicle components in water. The ex-vivo and in-vivo assessments showed satisfactory skin retention of LVC from optimum CCPCs. The histopathological assessment verified the safety of optimum CCPCs to be topically applied. Overall, the optimum CCPCs could be utilized as a potential system for the topical management of alopecia, with a prolonged period of activity, coupled with reduced LVC shortcomings.
{"title":"Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, <i>in- silico</i> and <i>in-vivo</i> studies.","authors":"Rofida Albash, Rania Moataz El-Dahmy, Mohammed I A Hamed, Khaled M Darwish, Abdulrahman M Alahdal, Amira B Kassem, Abdurrahman M Fahmy","doi":"10.1080/10717544.2022.2108939","DOIUrl":"https://doi.org/10.1080/10717544.2022.2108939","url":null,"abstract":"Abstract Levocetirizine hydrochloride (LVC) is an antihistaminic drug that is repurposed for the treatment of alopecia. This investigation is targeted for formulating LVC into cationic ceramide/phospholipid composite (CCPCs) for the management of alopecia. CCPCs were fabricated by ethanol-injection approach, through a central composite experiment. CCPCs were evaluated by inspecting their entrapment efficiency (EE%), polydispersity index (PDI), particle size (PS), and zeta potential (ZP). The optimum CCPCs were additionally studied by in-vitro, ex-vivo, in-silico, and in-vivo studies. The fabricated CCPCs had acceptable EE%, PS, PDI, and ZP values. The statistical optimization elected optimum CCPCs composed of 5 mg hyaluronic acid, 10 mg ceramide III, and 5 mg dimethyldidodecylammonium bromide employing phytantriol as a permeation enhancer. The optimum CCPCs had EE%, PS, PDI, and ZP of 88.36 ± 0.34%, 479.00 ± 50.34 nm, 0.377 ± 0.0035, and 20.20 ± 1.13 mV, respectively. The optimum CCPC maintained its stability for up to 90 days. It also viewed vesicles of tube shape via transmission electron microscope. The in-silico assessment resulted in better interaction and stability between LVC and vesicle components in water. The ex-vivo and in-vivo assessments showed satisfactory skin retention of LVC from optimum CCPCs. The histopathological assessment verified the safety of optimum CCPCs to be topically applied. Overall, the optimum CCPCs could be utilized as a potential system for the topical management of alopecia, with a prolonged period of activity, coupled with reduced LVC shortcomings.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40335523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.
{"title":"Recent trends in platelet membrane-cloaked nanoparticles for application of inflammatory diseases.","authors":"Zhengyu Fang, Jie Fang, Chunxiao Gao, Rui Gao, Peihong Lin, Wenying Yu","doi":"10.1080/10717544.2022.2117434","DOIUrl":"https://doi.org/10.1080/10717544.2022.2117434","url":null,"abstract":"<p><p>Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/a0/IDRD_29_2117434.PMC9448372.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isopropoxy benzene guanidine (IBG) is a novel substituted benzene guanidine analogue with antibacterial activity against multidrug-resistant bacteria. However, the bioavailability of IBG is not optimal due to its finite aqueous solubility, thus hampering its potential therapeutic exploitation. In this study, we prepared IBG/hydroxypropyl-β-CD (IBG/HP-β-CD) complex, and characterized it by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Physicochemical characterization indicated that the crystal morphology of IBG transformed into an amorphous state, thus forming IBG/HP-β-CD inclusion complexes. Complexation with HP-β-CD significantly improve the aqueous solubility, pharmaceutical properties, absorption, and bioavailability of IBG.
{"title":"Enhancement of the oral bioavailability of isopropoxy benzene guanidine though complexation with hydroxypropyl-β-cyclodextrin.","authors":"Yixing Lu, Liuye Yang, Wanying Zhang, Shiting Xie, Feifei Zhao, Xianfeng Peng, Zonghua Qin, Dongping Zeng, Zhenling Zeng","doi":"10.1080/10717544.2022.2118400","DOIUrl":"https://doi.org/10.1080/10717544.2022.2118400","url":null,"abstract":"<p><p>Isopropoxy benzene guanidine (IBG) is a novel substituted benzene guanidine analogue with antibacterial activity against multidrug-resistant bacteria. However, the bioavailability of IBG is not optimal due to its finite aqueous solubility, thus hampering its potential therapeutic exploitation. In this study, we prepared IBG/hydroxypropyl-β-CD (IBG/HP-β-CD) complex, and characterized it by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Physicochemical characterization indicated that the crystal morphology of IBG transformed into an amorphous state, thus forming IBG/HP-β-CD inclusion complexes. Complexation with HP-β-CD significantly improve the aqueous solubility, pharmaceutical properties, absorption, and bioavailability of IBG.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/66/fc/IDRD_29_2118400.PMC9448396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40348301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/10717544.2022.2122636
Jeehye Maeng, Kyunglim Lee
Our research group reported in 2011 the discovery of a novel cell-penetrating moiety in the N-terminus of the human translationally controlled tumor protein (TCTP). This moiety was responsible for the previously noted membrane translocating ability of purified full-length TCTP. The hydrophobic nature of TCTP-derived protein transduction domain (TCTP-PTD) endowed it with unique characteristics compared to other well-known cationic PTDs, such as TAT-PTD. TCTP-PTD internalizes partly through lipid-raft/caveolae-dependent endocytosis and partly by macropinocytosis. After cell entry, caveosome-laden TCTP-PTD appears to move to the cytoplasm and cytoskeleton except for the nucleus possibly through the movement to endoplasmic reticulum (ER). TCTP-PTD efficiently facilitates delivery of various types of cargos, such as peptides, proteins, and nucleic acids in vitro and in vivo. It is noteworthy that TCTP-PTD and its variants promote intranasal delivery of antidiabetics including, insulin and exendin-4 and of antigens for immunization in vivo, suggesting its potential for drug delivery. In this review, we attempted to describe recent advances in the understanding regarding the identification of TCTP-PTD, the characteristics of its cellular uptake, and the usefulness as a vehicle for delivery into cells of a variety of drugs and macromolecules. Our investigative efforts are continuing further to delineate the details of the functions and the regulatory mechanisms of TCTP-PTD-mediated cellular penetration and posttranslational modification of TCTP in physiologic and pathological processes. This is a review of what we currently know regarding TCTP-PTD and its use as a vehicle for the transduction of drugs and other molecules.
{"title":"Protein transduction domain of translationally controlled tumor protein: characterization and application in drug delivery.","authors":"Jeehye Maeng, Kyunglim Lee","doi":"10.1080/10717544.2022.2122636","DOIUrl":"https://doi.org/10.1080/10717544.2022.2122636","url":null,"abstract":"<p><p>Our research group reported in 2011 the discovery of a novel cell-penetrating moiety in the N-terminus of the human translationally controlled tumor protein (TCTP). This moiety was responsible for the previously noted membrane translocating ability of purified full-length TCTP. The hydrophobic nature of TCTP-derived protein transduction domain (TCTP-PTD) endowed it with unique characteristics compared to other well-known cationic PTDs, such as TAT-PTD. TCTP-PTD internalizes partly through lipid-raft/caveolae-dependent endocytosis and partly by macropinocytosis. After cell entry, caveosome-laden TCTP-PTD appears to move to the cytoplasm and cytoskeleton except for the nucleus possibly through the movement to endoplasmic reticulum (ER). TCTP-PTD efficiently facilitates delivery of various types of cargos, such as peptides, proteins, and nucleic acids in vitro and in vivo. It is noteworthy that TCTP-PTD and its variants promote intranasal delivery of antidiabetics including, insulin and exendin-4 and of antigens for immunization in vivo, suggesting its potential for drug delivery. In this review, we attempted to describe recent advances in the understanding regarding the identification of TCTP-PTD, the characteristics of its cellular uptake, and the usefulness as a vehicle for delivery into cells of a variety of drugs and macromolecules. Our investigative efforts are continuing further to delineate the details of the functions and the regulatory mechanisms of TCTP-PTD-mediated cellular penetration and posttranslational modification of TCTP in physiologic and pathological processes. This is a review of what we currently know regarding TCTP-PTD and its use as a vehicle for the transduction of drugs and other molecules.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40355474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs.
{"title":"Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review.","authors":"Bingqian Li, Huili Shao, Lei Gao, Huan Li, Huagang Sheng, Liqiao Zhu","doi":"10.1080/10717544.2022.2094498","DOIUrl":"https://doi.org/10.1080/10717544.2022.2094498","url":null,"abstract":"<p><p>Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/44/IDRD_29_2094498.PMC9275501.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40593971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/10717544.2022.2096711
Waad A Al-Otaibi, Sahar M AlMotwaa
Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.
{"title":"Oxaliplatin-loaded nanoemulsion containing <i>Teucrium polium</i> L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway.","authors":"Waad A Al-Otaibi, Sahar M AlMotwaa","doi":"10.1080/10717544.2022.2096711","DOIUrl":"https://doi.org/10.1080/10717544.2022.2096711","url":null,"abstract":"<p><p>Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing <i>Teucrium polium</i> L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (<i>p</i> ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40606298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-small cell lung cancer comprises 85% of the global lung cancer cases. Conventional chemotherapeutics possess certain limitations like systemic toxicity and drug resistance that requires the development of new therapeutic agents for successful treatment of lung cancer. Actinonin, a human peptide deformylase inhibitor, has demonstrated anti-cancerous properties in various leukemias and solid cancer types. However, it has limited therapeutic application because of its low bioavailability and systemic toxicity if administered in free form. This limitation can be overcome by using nano-delivery systems that will increase the therapeutic efficacy of actinonin. In the present study, human serum albumin actinonin nanoparticles were prepared using a desolvation technique and folic acid was conjugated to lysine residues of albumin for effective delivery to the lung. The lung adenocarcinoma model was established 24 weeks after intraperitoneal administration of urethane and chemotherapeutic efficacy of free as well as nanoencapsulated actinonin was evaluated. This study demonstrated anti-proliferative potential of folic acid conjugated human serum albumin nanoparticles encapsulating actinonin. The intraperitoneally administered nanoformulation exhibited sustain release profile of actinonin with longer half-life and mean retention time. The reduced dose frequency resulted in therapeutic efficacy comparable to free drug in vivo in terms of 100% survival and reduced tumor burden along with downregulation of epidermal growth factor receptor, folate receptor α and peptide deformylase expression in lung adenocarcinoma mice model. Therefore, actinonin encapsulated albumin nanoparticles-based therapy holds great potential as an alternative strategy to improve its anti-cancerous activity against lung adenocarcinoma.
{"title":"Therapeutic potential of human serum albumin nanoparticles encapsulated actinonin in murine model of lung adenocarcinoma.","authors":"Priyanca Ahlawat, Kanika Phutela, Amanjit Bal, Navneet Singh, Sadhna Sharma","doi":"10.1080/10717544.2022.2067600","DOIUrl":"https://doi.org/10.1080/10717544.2022.2067600","url":null,"abstract":"<p><p>Non-small cell lung cancer comprises 85% of the global lung cancer cases. Conventional chemotherapeutics possess certain limitations like systemic toxicity and drug resistance that requires the development of new therapeutic agents for successful treatment of lung cancer. Actinonin, a human peptide deformylase inhibitor, has demonstrated anti-cancerous properties in various leukemias and solid cancer types. However, it has limited therapeutic application because of its low bioavailability and systemic toxicity if administered in free form. This limitation can be overcome by using nano-delivery systems that will increase the therapeutic efficacy of actinonin. In the present study, human serum albumin actinonin nanoparticles were prepared using a desolvation technique and folic acid was conjugated to lysine residues of albumin for effective delivery to the lung. The lung adenocarcinoma model was established 24 weeks after intraperitoneal administration of urethane and chemotherapeutic efficacy of free as well as nanoencapsulated actinonin was evaluated. This study demonstrated anti-proliferative potential of folic acid conjugated human serum albumin nanoparticles encapsulating actinonin. The intraperitoneally administered nanoformulation exhibited sustain release profile of actinonin with longer half-life and mean retention time. The reduced dose frequency resulted in therapeutic efficacy comparable to free drug <i>in vivo</i> in terms of 100% survival and reduced tumor burden along with downregulation of epidermal growth factor receptor, folate receptor α and peptide deformylase expression in lung adenocarcinoma mice model. Therefore, actinonin encapsulated albumin nanoparticles-based therapy holds great potential as an alternative strategy to improve its anti-cancerous activity against lung adenocarcinoma.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40634927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/10717544.2022.2086941
Qiyan Wang, Zhipeng Dong, Fangning Lou, Yunxue Yin, Jiahao Zhang, Hanning Wen, Tao Lu, Yue Wang
The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy.
{"title":"Phenylboronic ester-modified polymeric nanoparticles for promoting TRP2 peptide antigen delivery in cancer immunotherapy.","authors":"Qiyan Wang, Zhipeng Dong, Fangning Lou, Yunxue Yin, Jiahao Zhang, Hanning Wen, Tao Lu, Yue Wang","doi":"10.1080/10717544.2022.2086941","DOIUrl":"10.1080/10717544.2022.2086941","url":null,"abstract":"<p><p>The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/e0/IDRD_29_2086941.PMC9248950.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}