PEGylated lipid nanoparticles (LNPs) are commonly used to deliver bioactive molecules, but the role of PEGylation in DNA-loaded LNP interactions at the cellular and subcellular levels remains poorly understood. In this study, we investigated the mechanism of action of DNA-loaded PEGylated LNPs using gene reporter technologies, dynamic light scattering (DLS), synchrotron small angle X-ray scattering (SAXS), and fluorescence confocal microscopy (FCS). We found that PEG has no significant impact on the size or nanostructure of DNA LNPs but reduces their zeta potential and interaction with anionic cell membranes. PEGylation increases the structural stability of LNPs and results in lower DNA unloading. FCS experiments revealed that PEGylated LNPs are internalized intact inside cells and largely shuttled to lysosomes, while unPEGylated LNPs undergo massive destabilization on the plasma membrane. These findings can inform the design, optimization, and validation of DNA-loaded LNPs for gene delivery and vaccine development.
{"title":"Investigating the mechanism of action of DNA-loaded PEGylated lipid nanoparticles","authors":"Luca Digiacomo PhD , Serena Renzi MSc , Erica Quagliarini PhD , Daniela Pozzi PhD , Heinz Amenitsch PhD , Gianmarco Ferri PhD , Luca Pesce PhD , Valentina De Lorenzi PhD , Giulia Matteoli MSc , Francesco Cardarelli PhD , Giulio Caracciolo (Prof.)","doi":"10.1016/j.nano.2023.102697","DOIUrl":"10.1016/j.nano.2023.102697","url":null,"abstract":"<div><p>PEGylated lipid nanoparticles (LNPs) are commonly used to deliver bioactive molecules, but the role of PEGylation in DNA-loaded LNP interactions at the cellular and subcellular levels remains poorly understood. In this study, we investigated the mechanism of action of DNA-loaded PEGylated LNPs using gene reporter technologies, dynamic light scattering (DLS), synchrotron small angle X-ray scattering (SAXS), and fluorescence confocal microscopy (FCS). We found that PEG has no significant impact on the size or nanostructure of DNA LNPs but reduces their zeta potential and interaction with anionic cell membranes. PEGylation increases the structural stability of LNPs and results in lower DNA unloading. FCS experiments revealed that PEGylated LNPs are internalized intact inside cells and largely shuttled to lysosomes, while unPEGylated LNPs undergo massive destabilization on the plasma membrane. These findings can inform the design, optimization, and validation of DNA-loaded LNPs for gene delivery and vaccine development.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"53 ","pages":"Article 102697"},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000485/pdfft?md5=67c4c107222b327ba2036e697171b843&pid=1-s2.0-S1549963423000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937475","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102693
Qian Chen PhD , Mengjuan Sun MD , Yanan Li PhD , Liping Huang PhD , Chang Zu PhD , Xiaoqin Kuang BD , Jianing Zhao BD , Mingyu Hao BD , Tingting Ma BD , Chunjiayu Li BD , Jiasheng Tu PhD , Chunmeng Sun PhD , Yunai Du PhD
Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment.
{"title":"Nano-vaccines combining customized in situ anti-PD-L1 depot for enhanced tumor immunotherapy","authors":"Qian Chen PhD , Mengjuan Sun MD , Yanan Li PhD , Liping Huang PhD , Chang Zu PhD , Xiaoqin Kuang BD , Jianing Zhao BD , Mingyu Hao BD , Tingting Ma BD , Chunjiayu Li BD , Jiasheng Tu PhD , Chunmeng Sun PhD , Yunai Du PhD","doi":"10.1016/j.nano.2023.102693","DOIUrl":"10.1016/j.nano.2023.102693","url":null,"abstract":"<div><p><span>Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic </span>cancer vaccines<span>, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy<span><span> by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes<span> (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean </span></span>phosphatidylcholine<span><span> (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and </span>intratumoral administration<span><span> of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for </span>tumor treatment.</span></span></span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"53 ","pages":"Article 102693"},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9983918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.nano.2023.102698
Olegi N. Kukaliia MD , Sergei V. Ageev MSc , Andrey V. Petrov MSc , Olga V. Kirik PhD , Dmitrii E. Korzhevskii PhD , Anatolii A. Meshcheriakov PhD , Anastasia A. Jakovleva PhD , Liudmila S. Poliakova PhD , Tatiana A. Novikova PhD , Maria E. Kolpakova PhD , Timur D. Vlasov DSc , Oleg E. Molchanov DSc , Dmitriy N. Maistrenko DSc , Igor V. Murin DSc , Vladimir V. Sharoyko DSc , Konstantin N. Semenov DSc
The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C60-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C60-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C60-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes.
{"title":"C60 adduct with L-arginine as a promising nanomaterial for treating cerebral ischemic stroke","authors":"Olegi N. Kukaliia MD , Sergei V. Ageev MSc , Andrey V. Petrov MSc , Olga V. Kirik PhD , Dmitrii E. Korzhevskii PhD , Anatolii A. Meshcheriakov PhD , Anastasia A. Jakovleva PhD , Liudmila S. Poliakova PhD , Tatiana A. Novikova PhD , Maria E. Kolpakova PhD , Timur D. Vlasov DSc , Oleg E. Molchanov DSc , Dmitriy N. Maistrenko DSc , Igor V. Murin DSc , Vladimir V. Sharoyko DSc , Konstantin N. Semenov DSc","doi":"10.1016/j.nano.2023.102698","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102698","url":null,"abstract":"<div><p><span><span><span>The work aimed to investigate the biocompatibility and </span>biological activity of the water-soluble </span>fullerene adduct C</span><sub>60</sub><span><span>-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of </span>neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C</span><sub>60</sub><span>-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C</span><sub>60</sub><span><span>-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in </span>Japan<span> for the treatment of ischemic and haemorrhagic strokes.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"53 ","pages":"Article 102698"},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92141685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. V. van Gent, Sylvia N. Kłodzińska, Maureen Severin, Muhanad Ali, Bjorn R van Doodewaerd, E. Bos, R. Koning, J. Drijfhout, H. M. Nielsen, P. Nibbering
The antimicrobial peptide Ab-Cath, is a promising candidate for development as treatment for antimicrobial resistant (AMR) bacterial infections. Future clinical use is hampered by Ab-Cath's cationic peptidic nature and limited therapeutic window. Here, we evaluated hyaluronic acid-based nanogels for encapsulation of Ab-Cath to circumvent these limitations. Using microfluidics, monodispersed anionic nanogels of 156 – 232 nm encapsulating >99 % Ab-Cath were prepared. Unprecedented, lyophilization using polyvinyl alcohol and dextran-40 provided Ab-Cath nanogel protection and allowed easy dose adjustment. Lyophilized and redispersed Ab-Cath nanogels were as effective as Ab-Cath solution in killing AMR Staphylococcus aureus , Acinetobacter baumannii and Escherichia coli in biological fluids, and in reducing S. aureus and A. baumannii biofilms. Importantly, encapsulation of Ab-Cath in nanogels reduced Ab-Cath's cytotoxic effects on human fibroblasts by ≥ 10-fold. Moreover, cutaneous application of Ab-Cath nanogels eliminated bacteria colonizing 3D human skin. These findings affirm the use of nanogels to increase the selectivity index of antimicrobial peptides.
{"title":"Encapsulation into hyaluronic acid-based nanogels improves the selectivity index of the snake cathelicidin Ab-Cath.","authors":"M. V. van Gent, Sylvia N. Kłodzińska, Maureen Severin, Muhanad Ali, Bjorn R van Doodewaerd, E. Bos, R. Koning, J. Drijfhout, H. M. Nielsen, P. Nibbering","doi":"10.2139/ssrn.4375055","DOIUrl":"https://doi.org/10.2139/ssrn.4375055","url":null,"abstract":"The antimicrobial peptide Ab-Cath, is a promising candidate for development as treatment for antimicrobial resistant (AMR) bacterial infections. Future clinical use is hampered by Ab-Cath's cationic peptidic nature and limited therapeutic window. Here, we evaluated hyaluronic acid-based nanogels for encapsulation of Ab-Cath to circumvent these limitations. Using microfluidics, monodispersed anionic nanogels of 156 – 232 nm encapsulating >99 % Ab-Cath were prepared. Unprecedented, lyophilization using polyvinyl alcohol and dextran-40 provided Ab-Cath nanogel protection and allowed easy dose adjustment. Lyophilized and redispersed Ab-Cath nanogels were as effective as Ab-Cath solution in killing AMR Staphylococcus aureus , Acinetobacter baumannii and Escherichia coli in biological fluids, and in reducing S. aureus and A. baumannii biofilms. Importantly, encapsulation of Ab-Cath in nanogels reduced Ab-Cath's cytotoxic effects on human fibroblasts by ≥ 10-fold. Moreover, cutaneous application of Ab-Cath nanogels eliminated bacteria colonizing 3D human skin. These findings affirm the use of nanogels to increase the selectivity index of antimicrobial peptides.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"46 1","pages":"102694"},"PeriodicalIF":5.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91127130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Chen, Ashleigh Williams, Edward B. Gordon, S. Rudolph, Brooke N. Longo, Gang Li, D. Kaplan
Micro- and nano-plastics (MPs and NPs) released from plastics in the environment can enter the food chain and target the human intestine. However, knowledge about the effects of these particles on the human intestine is still limited due to the lack of relevant human intestinal models to validate data obtained from animal studies or tissue models employing cancer cells. In this study, human intestinal organoids were used to develop epithelia to mimic the cell complexity and functions of native tissue. Microfold cells (M cells) were induced to distinguish their role when exposure to MPs and NPs. During the exposure, the M cells acted as sensors, capturers and transporters of larger sized particles. The epithelial cells internalized the particles in a size-, concentration-, and time-dependent manner. Importantly, high concentrations of particles significantly triggered the secretion of a panel of inflammatory cytokines linked to human inflammatory bowel disease (IBD).
{"title":"Biological effects of polystyrene micro- and nano-plastics on human intestinal organoid-derived epithelial tissue models without and with M cells.","authors":"Ying Chen, Ashleigh Williams, Edward B. Gordon, S. Rudolph, Brooke N. Longo, Gang Li, D. Kaplan","doi":"10.2139/ssrn.4330040","DOIUrl":"https://doi.org/10.2139/ssrn.4330040","url":null,"abstract":"Micro- and nano-plastics (MPs and NPs) released from plastics in the environment can enter the food chain and target the human intestine. However, knowledge about the effects of these particles on the human intestine is still limited due to the lack of relevant human intestinal models to validate data obtained from animal studies or tissue models employing cancer cells. In this study, human intestinal organoids were used to develop epithelia to mimic the cell complexity and functions of native tissue. Microfold cells (M cells) were induced to distinguish their role when exposure to MPs and NPs. During the exposure, the M cells acted as sensors, capturers and transporters of larger sized particles. The epithelial cells internalized the particles in a size-, concentration-, and time-dependent manner. Importantly, high concentrations of particles significantly triggered the secretion of a panel of inflammatory cytokines linked to human inflammatory bowel disease (IBD).","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"2 1","pages":"102680"},"PeriodicalIF":5.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85487444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rayhanul Islam, Kevin Kotalík, V. Šubr, Shanghui Gao, Jian-Rong Zhou, K. Yokomizo, T. Etrych, Jun Fang
In this study, we developed a nanoformulation of 5-aminolevulinic acid (5-ALA) for tumor-targeted photodynamic therapy, in which 5-ALA was conjugated with a biocompatible polymer N-(2-hydroxypropyl)methacrylamide (HPMA) through the hydrazone bond, i.e., P-ALA. P-ALA behaves as the nano-sized molecule with an average size of 5.5 nm in aqueous solution. P-ALA shows a largely increased release rate in acidic pH than physiological pH, suggesting the rapid release profile in acidic tumor environment. P-ALA did not show apparent cytotoxicity up to 0.1 mg/ml, however, under light irradiation, remarkable cell death was induced with the IC50 of 20-30 μg/ml. More importantly, we found significantly higher tumor accumulation of P-ALA than 5-ALA which benefit from its nano-size by taking advantage of the enhanced permeability and retention (EPR) effect. Consequently, P-ALA exhibited much improved in vivo antitumor efficacy without any apparent side effects. We thus anticipate the application of P-ALA as a nano-designed photosensitizer for anticancer photodynamic therapy.
{"title":"HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.","authors":"Rayhanul Islam, Kevin Kotalík, V. Šubr, Shanghui Gao, Jian-Rong Zhou, K. Yokomizo, T. Etrych, Jun Fang","doi":"10.2139/ssrn.4247655","DOIUrl":"https://doi.org/10.2139/ssrn.4247655","url":null,"abstract":"In this study, we developed a nanoformulation of 5-aminolevulinic acid (5-ALA) for tumor-targeted photodynamic therapy, in which 5-ALA was conjugated with a biocompatible polymer N-(2-hydroxypropyl)methacrylamide (HPMA) through the hydrazone bond, i.e., P-ALA. P-ALA behaves as the nano-sized molecule with an average size of 5.5 nm in aqueous solution. P-ALA shows a largely increased release rate in acidic pH than physiological pH, suggesting the rapid release profile in acidic tumor environment. P-ALA did not show apparent cytotoxicity up to 0.1 mg/ml, however, under light irradiation, remarkable cell death was induced with the IC50 of 20-30 μg/ml. More importantly, we found significantly higher tumor accumulation of P-ALA than 5-ALA which benefit from its nano-size by taking advantage of the enhanced permeability and retention (EPR) effect. Consequently, P-ALA exhibited much improved in vivo antitumor efficacy without any apparent side effects. We thus anticipate the application of P-ALA as a nano-designed photosensitizer for anticancer photodynamic therapy.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"265 1","pages":"102636"},"PeriodicalIF":5.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77497969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liver injury caused by hepatitis is the pathological basis of varied hepatic diseases with high morbidity and mortality. Although siRNA appears promising in therapeutics of hepatitis, efficient and safe delivery remains a challenge. In this study, we developed a new strategy of incorporating glycyrrhizic acid (GA) and polyene phosphatidylcholine (PPC) into lipid nanoparticles (GA/PPC-modified LNPs), which was capable of promoting cellular uptake, enhancing gene-silencing, reducing cytotoxicity and improving siRNA stability. GA/PPC-modified LNP and siRNA lipoplex targeting NF-κB, a key mediator of inflammation, mitigates acute liver injury, as assessed by liver histology, hematological and pro-inflammatory cytokine analysis. Furthermore, GA/PPC-modified LNPs reveal efficiently intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting viral infection. In conclusion, GA/PPC-modified LNPs could be used as a promising delivery system for nucleic acid-based therapy.
{"title":"Incorporation of glycyrrhizic acid and polyene phosphatidylcholine in lipid nanoparticles ameliorates acute liver injury via delivering p65 siRNA.","authors":"Qiming Yin, Xiangling Song, Peng-fei Yang, Wen Yang, Xinyu Li, Xuejun Wang, Shengnan Wang","doi":"10.2139/ssrn.4096906","DOIUrl":"https://doi.org/10.2139/ssrn.4096906","url":null,"abstract":"Liver injury caused by hepatitis is the pathological basis of varied hepatic diseases with high morbidity and mortality. Although siRNA appears promising in therapeutics of hepatitis, efficient and safe delivery remains a challenge. In this study, we developed a new strategy of incorporating glycyrrhizic acid (GA) and polyene phosphatidylcholine (PPC) into lipid nanoparticles (GA/PPC-modified LNPs), which was capable of promoting cellular uptake, enhancing gene-silencing, reducing cytotoxicity and improving siRNA stability. GA/PPC-modified LNP and siRNA lipoplex targeting NF-κB, a key mediator of inflammation, mitigates acute liver injury, as assessed by liver histology, hematological and pro-inflammatory cytokine analysis. Furthermore, GA/PPC-modified LNPs reveal efficiently intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting viral infection. In conclusion, GA/PPC-modified LNPs could be used as a promising delivery system for nucleic acid-based therapy.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"10 1","pages":"102649"},"PeriodicalIF":5.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86972823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farah Shahjin, Milankumar Patel, Mahmudul Hasan, Jacob D. Cohen, Farhana Islam, Md Ashaduzzaman, Mohammad Ullah Nayan, Mahadevan Subramaniam, You Zhou, Irene Andreu, H. Gendelman, B. Kevadiya
Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms.
{"title":"Development of a porous layer-by-layer microsphere with branched aliphatic hydrocarbon porogens.","authors":"Farah Shahjin, Milankumar Patel, Mahmudul Hasan, Jacob D. Cohen, Farhana Islam, Md Ashaduzzaman, Mohammad Ullah Nayan, Mahadevan Subramaniam, You Zhou, Irene Andreu, H. Gendelman, B. Kevadiya","doi":"10.2139/ssrn.4189034","DOIUrl":"https://doi.org/10.2139/ssrn.4189034","url":null,"abstract":"Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"13 19 1","pages":"102644"},"PeriodicalIF":5.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80615598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advances in bioinformatics and nanotechnology offer great opportunities for personalized cancer vaccine development. However, the timely identification of neoantigens and unsatisfactory efficacy of therapeutic cancer vaccines remain two obstacles for clinical transformation. We propose a "prime and boost" strategy to facilitate neoantigen-based immunotherapy. To prime the immune system, we first constructed personalized liposomes with cancer cell membranes and adjuvant R848 to provide immunostimulatory efficacy and time for identifying tumor antigens. Liposomes loaded with personalized neopeptides and adjuvants were used to boost the immune response. In vitro experiments verified potent immune responses, including macrophage polarization, dendritic cell maturation, and T lymphocyte activation. In vivo B16F10 and TC-1 cancer model were used to investigate efficient tumor growth suppression. Liposomal vaccines with neopeptides could stimulate human dendritic cells and T lymphocytes in vitro. These results demonstrate that the "prime and boost" strategy provides simple, quick, and efficient personalized vaccines for cancer therapy.
{"title":"Cell membrane-camouflaged liposomes and neopeptide-loaded liposomes with TLR agonist R848 provides a prime and boost strategy for efficient personalized cancer vaccine therapy.","authors":"Lu Shi, H. Gu","doi":"10.2139/ssrn.4251197","DOIUrl":"https://doi.org/10.2139/ssrn.4251197","url":null,"abstract":"Recent advances in bioinformatics and nanotechnology offer great opportunities for personalized cancer vaccine development. However, the timely identification of neoantigens and unsatisfactory efficacy of therapeutic cancer vaccines remain two obstacles for clinical transformation. We propose a \"prime and boost\" strategy to facilitate neoantigen-based immunotherapy. To prime the immune system, we first constructed personalized liposomes with cancer cell membranes and adjuvant R848 to provide immunostimulatory efficacy and time for identifying tumor antigens. Liposomes loaded with personalized neopeptides and adjuvants were used to boost the immune response. In vitro experiments verified potent immune responses, including macrophage polarization, dendritic cell maturation, and T lymphocyte activation. In vivo B16F10 and TC-1 cancer model were used to investigate efficient tumor growth suppression. Liposomal vaccines with neopeptides could stimulate human dendritic cells and T lymphocytes in vitro. These results demonstrate that the \"prime and boost\" strategy provides simple, quick, and efficient personalized vaccines for cancer therapy.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"114 1","pages":"102648"},"PeriodicalIF":5.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88067350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. K. Samani, Fatemeh Maghsoudinia, Fatemeh Mehradnia, S. Hejazi, M. Saeb, Tayebe Sobhani, Zohreh Farahbakhsh, M. Mehrgardi, M. Tavakoli
Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer.
{"title":"Ultrasound-guided chemoradiotherapy of breast cancer using smart methotrexate-loaded perfluorohexane nanodroplets.","authors":"R. K. Samani, Fatemeh Maghsoudinia, Fatemeh Mehradnia, S. Hejazi, M. Saeb, Tayebe Sobhani, Zohreh Farahbakhsh, M. Mehrgardi, M. Tavakoli","doi":"10.2139/ssrn.4210211","DOIUrl":"https://doi.org/10.2139/ssrn.4210211","url":null,"abstract":"Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer.","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"40 1","pages":"102643"},"PeriodicalIF":5.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76743569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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