Pub Date : 2023-04-01DOI: 10.1016/j.nano.2023.102658
Yunuo Zheng M.S. , Bo Jiang M.S. , Hongmei Guo B.S. , Zhonghai Zhang M.S. , Bo Chen Ph.D. , Zhengkui Zhang Ph.D. , Shaoyuan Wu Ph.D. , Jiaojiao Zhao Ph.D.
Angiogenesis plays a key role in the progression and metastasis of melanoma, and the pro-angiogenic effect of macrophages is one major reason for the failure of current anti-angiogenic therapies. Here, a nano-immunotherapy combining ferumoxytol and poly(I:C) (ferumoxytol/poly(I:C)) has been developed to boost the anti-angiogenic activities of macrophages to inhibit melanoma. Our findings demonstrated that ferumoxytol/poly(I:C) was a highly efficacious anti-tumor therapy with limited toxicity. Both in vivo and in vitro experiments indicated that this combination was successful in impeding angiogenesis. Ferumoxytol/poly(I:C) was demonstrated to reduce the viability of endothelial cells, thus hindering tube formation. Particularly, ferumoxytol/poly(I:C) was able to polarize macrophages to the M1 phenotype and decrease the expression of vascular endothelial growth factor, which in turn amplified the anti-angiogenic properties of ferumoxytol/poly(I:C). This combination of ferumoxytol/poly(I:C) nano-immunotherapy enriches the anti-angiogenic therapeutic nature of ferumoxytol and will shed new light on the treatment of melanoma.
{"title":"The combinational nano-immunotherapy of ferumoxytol and poly(I:C) inhibits melanoma via boosting anti-angiogenic immunity","authors":"Yunuo Zheng M.S. , Bo Jiang M.S. , Hongmei Guo B.S. , Zhonghai Zhang M.S. , Bo Chen Ph.D. , Zhengkui Zhang Ph.D. , Shaoyuan Wu Ph.D. , Jiaojiao Zhao Ph.D.","doi":"10.1016/j.nano.2023.102658","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102658","url":null,"abstract":"<div><p><span><span>Angiogenesis<span> plays a key role in the progression and metastasis of </span></span>melanoma<span>, and the pro-angiogenic effect of macrophages is one major reason for the failure of current anti-angiogenic therapies. Here, a nano-immunotherapy combining ferumoxytol and poly(I:C) (ferumoxytol/poly(I:C)) has been developed to boost the anti-angiogenic activities of macrophages to inhibit melanoma. Our findings demonstrated that ferumoxytol/poly(I:C) was a highly efficacious anti-tumor therapy with limited toxicity. Both </span></span><em>in vivo</em> and <em>in vitro</em><span> experiments indicated that this combination was successful in impeding angiogenesis. Ferumoxytol/poly(I:C) was demonstrated to reduce the viability of endothelial cells<span>, thus hindering tube formation. Particularly, ferumoxytol/poly(I:C) was able to polarize macrophages to the M1 phenotype and decrease the expression of vascular endothelial growth factor, which in turn amplified the anti-angiogenic properties of ferumoxytol/poly(I:C). This combination of ferumoxytol/poly(I:C) nano-immunotherapy enriches the anti-angiogenic therapeutic nature of ferumoxytol and will shed new light on the treatment of melanoma.</span></span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3341945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1016/j.nano.2023.102660
Binbin Liang PhD , Yuhang Miao MSc , Liying Zhao MSc , Lan Fang PhD , Dawei Deng PhD
The synergistic effect of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like nanomedicine (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic β-cyclodextrins (β-CD) doped lipid-based vesicles as the core (receptacle) and β-CD modified camptothecin (CPT) pro-drug as the flyable dandelion seeds. The β-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular β-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the internalization into cancer cells. CPT interacted with β-CD through glutathione (GSH)-cleavable disulfide bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.
{"title":"A dandelion-like nanomedicine via hierarchical self-assembly for synergistic chemotherapy and photo-dynamic cancer therapy","authors":"Binbin Liang PhD , Yuhang Miao MSc , Liying Zhao MSc , Lan Fang PhD , Dawei Deng PhD","doi":"10.1016/j.nano.2023.102660","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102660","url":null,"abstract":"<div><p><span><span>The synergistic effect<span><span> of chemotherapy and photo-dynamic therapy (PDT) is an effective way to improve the efficiency of tumor treatment. However, most synergistic therapeutic </span>drugs have poor water solubility and stability, so it is difficult to achieve high therapeutic effects while avoiding the severe side effects. Herein, a unique dandelion-like </span></span>nanomedicine<span><span><span><span> (named as cRGDfk-CCPT-mCe6) was successfully synthesized using Ce6-loaded amphiphilic β-cyclodextrins (β-CD) doped lipid-based vesicles as the core (receptacle) and β-CD modified camptothecin<span> (CPT) pro-drug as the flyable dandelion seeds. The β-CD modified CPT pro-drug was introduced into the core vesicles in succession via host-guest interaction between inter-molecular β-CD and CPT, and cRGDfk peptides were further introduced as the outermost layer (stigma) to enhance the </span></span>internalization into </span>cancer cells. CPT interacted with β-CD through </span>glutathione (GSH)-cleavable </span></span>disulfide<span><span> bonds, which led to drug release in glutathione-rich cancer cells, just as spread of dandelion seeds in the wind. GSH consumption further disrupted the intracellular redox homeostasis<span> of cancer cells through combined action of Ce6 with light irradiation and the synergistic anti-tumor effect was thus achieved, resulting in </span></span>apoptosis of cancer cells. Therefore, the nanomedicine provides a facile and versatile anti-tumor strategy, as well as a persistent anti-cancer effects.</span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1567232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-01DOI: 10.1016/j.nano.2023.102659
Riku Kawasaki Ph. D. , Hidetoshi Hirano , Keita Yamana , Hinata Isozaki , Shogo Kawamura , Yu Sanada Ph. D. , Kaori Bando , Anri Tabata , Kouhei Yoshikawa , Hideki Azuma Ph. D. , Takushi Takata Ph. D. , Hiroki Tanaka Ph.D. , Yoshinori Sakurai Ph. D. , Minoru Suzuki M. D. , Naoki Tarutani Ph. D. , Kiyofumi Katagiri Ph. D. , Shin-ichi Sawada Ph. D. , Yoshihiro Sasaki Ph. D. , Kazunari Akiyoshi Ph. D. , Takeshi Nagasaki Ph. D. , Atsushi Ikeda Ph. D.
Boron neutron capture therapy shows is a promising approach to cancer therapy, but the delivery of effective boron agents is challenging. To address the requirements for efficient boron delivery, we used a hybrid nanoparticle comprising a carborane = bearing pullulan nanogel and hydrophobized boron oxide nanoparticle (HBNGs) enabling the preparation of highly concentrated boron agents for efficient delivery. The HBNGs showed better anti-cancer effects on Colon26 cells than a clinically boron agent, L-BPA/fructose complex, by enhancing the accumulation and retention amount of the boron agent within cells in vitro. The accumulation of HBNGs in tumors, due to the enhanced permeation and retention effect, enabled the delivery of boron agents with high tumor selectivity, meeting clinical demands. Intravenous injection of boron neutron capture therapy (BNCT) using HBNGs decreased tumor volume without significant body weight loss, and no regrowth of tumor was observed three months after complete regression. The therapeutic efficacy of HBNGs was better than that of L-BPA/fructose complex. BNCT with HBNGs is a promising approach to cancer therapeutics.
{"title":"Carborane bearing pullulan nanogel-boron oxide nanoparticle hybrid for boron neutron capture therapy","authors":"Riku Kawasaki Ph. D. , Hidetoshi Hirano , Keita Yamana , Hinata Isozaki , Shogo Kawamura , Yu Sanada Ph. D. , Kaori Bando , Anri Tabata , Kouhei Yoshikawa , Hideki Azuma Ph. D. , Takushi Takata Ph. D. , Hiroki Tanaka Ph.D. , Yoshinori Sakurai Ph. D. , Minoru Suzuki M. D. , Naoki Tarutani Ph. D. , Kiyofumi Katagiri Ph. D. , Shin-ichi Sawada Ph. D. , Yoshihiro Sasaki Ph. D. , Kazunari Akiyoshi Ph. D. , Takeshi Nagasaki Ph. D. , Atsushi Ikeda Ph. D.","doi":"10.1016/j.nano.2023.102659","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102659","url":null,"abstract":"<div><p><span><span>Boron neutron capture therapy<span><span> shows is a promising approach to cancer therapy, but the delivery of effective boron agents is challenging. To address the requirements for efficient boron delivery, we used a hybrid nanoparticle comprising a carborane = bearing </span>pullulan </span></span>nanogel and hydrophobized boron oxide nanoparticle (HBNGs) enabling the preparation of highly concentrated boron agents for efficient delivery. The HBNGs showed better anti-cancer effects on Colon26 cells than a clinically boron agent, L-BPA/fructose complex, by enhancing the accumulation and retention amount of the boron agent within cells </span><em>in vitro</em><span>. The accumulation of HBNGs in tumors, due to the enhanced permeation<span> and retention effect, enabled the delivery of boron agents with high tumor selectivity, meeting clinical demands. Intravenous injection<span><span> of boron neutron capture therapy (BNCT) using HBNGs decreased tumor volume without significant body weight loss, and no </span>regrowth of tumor was observed three months after complete regression. The therapeutic efficacy of HBNGs was better than that of L-BPA/fructose complex. BNCT with HBNGs is a promising approach to cancer therapeutics.</span></span></span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1567233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102636
Rayhanul Islam Ph.D. , Kevin Kotalík BSc. , Vladimír Šubr Ph.D. , Shanghui Gao M.Sc. , Jian-Rong Zhou Ph.D. , Kazumi Yokomizo Ph.D. , Tomáš Etrych Ph.D., DSc. , Jun Fang Ph.D., M.D.
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 Ph.D. , Kevin Kotalík BSc. , Vladimír Šubr Ph.D. , Shanghui Gao M.Sc. , Jian-Rong Zhou Ph.D. , Kazumi Yokomizo Ph.D. , Tomáš Etrych Ph.D., DSc. , Jun Fang Ph.D., M.D.","doi":"10.1016/j.nano.2022.102636","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102636","url":null,"abstract":"<div><p>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 <em>N</em>-(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 IC<sub>50</sub> 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.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3021362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102630
Pilei Si PhD , Wenyan Yu PhD , Chengzhen Li M.M. , Haijun Chen M.M. , Enzhao Zhang M.M. , Jiaojiao Gu M.M. , Ruoyan Wang M.M. , Jinjin Shi PhD
The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2′-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.
{"title":"Oxygen-independent alkyl radical nanogenerator enhances breast cancer therapy","authors":"Pilei Si PhD , Wenyan Yu PhD , Chengzhen Li M.M. , Haijun Chen M.M. , Enzhao Zhang M.M. , Jiaojiao Gu M.M. , Ruoyan Wang M.M. , Jinjin Shi PhD","doi":"10.1016/j.nano.2022.102630","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102630","url":null,"abstract":"<div><p><span><span><span><span>The hypoxic microenvironment<span> of breast cancer substantially reduces oxygen-dependent free radical generation. </span></span>Overexpression of </span>glutathione<span> (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2′-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical </span></span>treatment. </span><em>In vivo</em> and <em>in vitro</em> assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3210032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102649
Qiming Yin PhD , Xiang Song PhD , Peng Yang MSc , Wen Yang MSc , Xinyu Li BSc , Xuejun Wang PhD , Shengqi Wang PhD
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 PhD , Xiang Song PhD , Peng Yang MSc , Wen Yang MSc , Xinyu Li BSc , Xuejun Wang PhD , Shengqi Wang PhD","doi":"10.1016/j.nano.2022.102649","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102649","url":null,"abstract":"<div><p><span><span>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 </span>glycyrrhizic acid<span><span><span><span> (GA) and polyene </span>phosphatidylcholine<span> (PPC) into lipid<span> 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 </span></span></span>lipoplex targeting NF-κB, a key mediator of inflammation, mitigates acute liver injury, as assessed by </span>liver histology<span>, hematological and pro-inflammatory cytokine analysis. Furthermore, GA/PPC-modified LNPs reveal efficiently intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting </span></span></span>viral infection. In conclusion, GA/PPC-modified LNPs could be used as a promising delivery system for nucleic acid-based therapy.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"2377484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102648
Lu Shi PhD, Hongchen Gu PhD
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 PhD, Hongchen Gu PhD","doi":"10.1016/j.nano.2022.102648","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102648","url":null,"abstract":"<div><p><span>Recent advances in bioinformatics and nanotechnology offer great opportunities for personalized cancer vaccine<span> development. However, the timely identification of neoantigens<span><span><span> 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 </span>liposomes<span> with cancer cell membranes and adjuvant </span></span>R848<span> to provide immunostimulatory efficacy and time for identifying tumor antigens. Liposomes loaded with personalized neopeptides and adjuvants were used to boost the immune response. </span></span></span></span><em>In vitro</em><span> experiments verified potent immune responses, including macrophage polarization<span>, dendritic cell maturation, and T lymphocyte activation. </span></span><em>In vivo</em> 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 <em>in vitro</em>. These results demonstrate that the “prime and boost” strategy provides simple, quick, and efficient personalized vaccines for cancer therapy.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1567237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2023.102653
Carlos M. Valdemar-Aguilar MSc , Ravichandran Manisekaran PhD , Laura S. Acosta-Torres PhD , Luz M. López-Marín PhD
Tuberculosis (TB), historically the most significant cause of human morbidity and mortality, has returned as the top infectious disease worldwide, under circumstances worsened by the COVID-19 pandemic's devastating effects on public health. Although Mycobacterium tuberculosis, the causal agent, has been known of for more than a century, the development of tools to control it has been largely neglected. With the advancement of nanotechnology, the possibility of engineering tools at the nanoscale creates unique opportunities to exploit any molecular type. However, little attention has been paid to one of the major attributes of the pathogen, represented by the atypical coat and its abundant lipids. In this review, an overview of the lipids encountered in M. tuberculosis and interest in exploiting them for the development of TB control tools are presented. Then, the amalgamation of nanotechnology with mycobacterial lipids from both reported and future works are discussed.
{"title":"Spotlight on mycobacterial lipid exploitation using nanotechnology for diagnosis, vaccines, and treatments","authors":"Carlos M. Valdemar-Aguilar MSc , Ravichandran Manisekaran PhD , Laura S. Acosta-Torres PhD , Luz M. López-Marín PhD","doi":"10.1016/j.nano.2023.102653","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102653","url":null,"abstract":"<div><p>Tuberculosis (TB), historically the most significant cause of human morbidity and mortality, has returned as the top infectious disease worldwide, under circumstances worsened by the COVID-19 pandemic's devastating effects on public health. Although <em>Mycobacterium tuberculosis</em>, the causal agent, has been known of for more than a century, the development of tools to control it has been largely neglected. With the advancement of nanotechnology, the possibility of engineering tools at the nanoscale creates unique opportunities to exploit any molecular type. However, little attention has been paid to one of the major attributes of the pathogen, represented by the atypical coat and its abundant lipids. In this review, an overview of the lipids encountered in <em>M. tuberculosis</em> and interest in exploiting them for the development of TB control tools are presented. Then, the amalgamation of nanotechnology with mycobacterial lipids from both reported and future works are discussed.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3021359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peptosomes, as a vesicular polypeptide-based system and a versatile carrier for co-delivery of hydrophilic and hydrophobic materials, provide great delivery opportunities due to the intrinsic biocompatibility and biodegradability of the polypeptides backbone. In the current study, a novel poly(L-glutamic acid)-block-polylactic acid di-block copolymer (PGA-PLA) was synthesized in two steps. Firstly, γ-benzyl L-glutamate-N-carboxy anhydride (BLG-NCA) and 3,6-dimethyl-1,4-dioxane-2,5-dione were polymerized using N-hexylamine and benzyl alcohol as initiators to produce poly(γ-benzyl L-glutamate (PBLG) and polylactic acid. Then, PBLG was deprotected to produce PGA. Secondly, PGA was conjugated to the benzyl-PLGA to fabricate PGA-PLA diblock copolymer. The synthesized diblock copolymer was used for the encapsulation of doxorubicin, as hydrophilic anticancer and ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) as hydrophobic contrast agent within aqueous core and bilayer of vesicular peptosome, respectively via double emulsion method. The prepared peptosomes (Pep@USPIONs-DOX) controlled the release of DOX (<15 % of the encapsulated DOX release up to 240 h of incubation at the physiological conditions) while increasing the stability and solubility of the hydrophobic USPIONs. Then, AS1411 DNA aptamer was decorated on the surface of the PGA-PLA peptosomes (Apt-Pep@USPIONs-DOX). The prepared targeted and non-targeted platforms showed spherical morphology with hydrodynamic sizes of 265 ± 52 and 229 ± 44 nm respectively. In vitro cellular cytotoxicity and cellular uptake were studied in nucleolin positive (4T1) and nucleolin negative (CHO) cell lines. Cellular uptake of the targeted formulation was greater than that of non-targeted peptosome, while cellular internalization of these peptosomes was identical in CHO cells. Moreover, targeted peptosomes showed greater toxicity than non-targeted peptosome in 4T1 cell line. The prepared theranostic targeted peptosomes demonstrated improved capability in terms of survival rate, biodistribution, tumor suppression efficiency, and MR imaging in the 4T1 tumor-bearing mice.
肽体作为一种以囊泡多肽为基础的系统,是一种多用途的载体,用于亲疏水材料的共递送,由于多肽主链固有的生物相容性和可生物降解性,提供了很大的递送机会。本研究分两步合成了一种新型聚l -谷氨酸嵌段聚乳酸二嵌段共聚物(PGA-PLA)。首先,以n -己胺和苯甲醇为引发剂,对γ-苄基谷氨酸- n -羧基酸酐(BLG-NCA)和3,6-二甲基-1,4-二恶烷-2,5-二酮进行聚合,制备聚γ-苄基谷氨酸(PBLG)和聚乳酸。然后将PBLG去保护生成PGA。其次,将PGA与苄基plga偶联制备PGA- pla二嵌段共聚物。将合成的二嵌段共聚物分别用双乳液法将阿霉素作为亲水性抗癌剂和超小超顺磁性氧化铁纳米颗粒(USPIONs)作为疏水造影剂包封在囊泡型蛋白酶体的水核和双层内。制备的肽体(Pep@USPIONs-DOX)控制DOX的释放(生理条件下240 h内,约占包封DOX释放量的15%),同时提高疏水uspion的稳定性和溶解度。然后,将AS1411 DNA适体修饰在PGA-PLA酶体表面(Apt-Pep@USPIONs-DOX)。制备的靶平台和非靶平台均为球形,水动力尺寸分别为265±52 nm和229±44 nm。研究了核仁蛋白阳性(4T1)和核仁蛋白阴性(CHO)细胞株的体外细胞毒性和细胞摄取。靶向制剂的细胞摄取大于非靶向肽体,而这些肽体的细胞内化在CHO细胞中是相同的。此外,在4T1细胞系中,靶向酶体比非靶向酶体表现出更大的毒性。制备的靶向治疗性肽体在4T1荷瘤小鼠的存活率、生物分布、抑瘤效率和MR成像方面均有改善。
{"title":"Targeted poly(L-glutamic acid)-based hybrid peptosomes co-loaded with doxorubicin and USPIONs as a theranostic platform for metastatic breast cancer","authors":"Maliheh Hasannia PhD , Kamran Lamei PhD , Khalil Abnous PhD , Seyed Mohammad Taghdisi PhD , Sirous Nekooei MD, PhD , Negar Nekooei MD , Mohammad Ramezani PhD , Mona Alibolandi PhD","doi":"10.1016/j.nano.2022.102645","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102645","url":null,"abstract":"<div><p><span><span><span>Peptosomes, as a vesicular polypeptide-based system and a versatile carrier for co-delivery of hydrophilic<span> and hydrophobic materials, provide great delivery opportunities due to the intrinsic biocompatibility<span><span> and biodegradability of the polypeptides </span>backbone. In the current study, a novel poly(L-glutamic acid)-block-polylactic acid di-block </span></span></span>copolymer (PGA-PLA) was synthesized in two steps. Firstly, γ-benzyl L-glutamate-N-carboxy </span>anhydride<span><span><span> (BLG-NCA) and 3,6-dimethyl-1,4-dioxane-2,5-dione were polymerized using N-hexylamine and benzyl alcohol<span> as initiators to produce poly(γ-benzyl L-glutamate (PBLG) and polylactic acid. Then, PBLG was deprotected to produce PGA. Secondly, PGA was conjugated to the benzyl-PLGA to fabricate PGA-PLA diblock copolymer. The synthesized diblock copolymer was used for the encapsulation of </span></span>doxorubicin, as hydrophilic anticancer and ultra-small superparamagnetic iron oxide </span>nanoparticles<span> (USPIONs) as hydrophobic contrast agent within aqueous core and bilayer of vesicular peptosome, respectively </span></span></span><em>via</em><span><span> double emulsion method. The prepared peptosomes (Pep@USPIONs-DOX) controlled the release of DOX (<15 % of the encapsulated DOX release up to 240 h of incubation at the physiological conditions) while increasing the stability and solubility of the hydrophobic USPIONs. Then, AS1411 </span>DNA<span><span><span> aptamer was decorated on the surface of the PGA-PLA peptosomes (Apt-Pep@USPIONs-DOX). The prepared targeted and non-targeted platforms showed spherical morphology with </span>hydrodynamic sizes of 265 ± 52 and 229 ± 44 </span>nm respectively. </span></span><em>In vitro</em><span> cellular cytotoxicity<span><span> and cellular uptake were studied in nucleolin<span> positive (4T1) and nucleolin negative (CHO) cell lines. Cellular uptake of the targeted formulation was greater than that of non-targeted peptosome, while cellular internalization of these peptosomes was identical in </span></span>CHO<span> cells. Moreover, targeted peptosomes showed greater toxicity than non-targeted peptosome in 4T1 cell line<span>. The prepared theranostic targeted peptosomes demonstrated improved capability in terms of survival rate, biodistribution, tumor suppression efficiency, and MR imaging in the 4T1 tumor-bearing mice.</span></span></span></span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3342721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102633
Ariane Mwema M BBMC , Pauline Bottemanne PhD , Adrien Paquot M FARM , Bernard Ucakar Bachelor , Kevin Vanvarenberg Bachelor , Mireille Alhouayek PhD , Giulio G. Muccioli PhD , Anne des Rieux PhD
Here, prostaglandin D2-glycerol ester (PGD2-G) was selected to target neuroinflammation. As PGD2-G is reported to have a short plasmatic half-life, we propose to use lipid nanocapsules (LNC) as vehicle to safely transport PGD2-G to the central nervous system (CNS). PGD2-G-loaded LNC (PGD2-G-LNC) reduced pro-inflammatory cytokine expression in activated microglial cells, even so after crossing a primary olfactory cell monolayer. A single nasal administration of PGD2-G-LNC in lipopolysaccharide (LPS)-treated mice reduced pro-inflammatory cytokine expression in the olfactory bulb. Coating LNC's surface with a cell-penetrating peptide, transactivator of transcription (TAT), increased its accumulation in the brain. Although TAT-coated PGD2-G-LNC modestly exerted its anti-inflammatory effect in a mouse model of multiple sclerosis similar to free PGD2-G after nasal administration, TAT-coated LNC surprisingly reduced the expression of pro-inflammatory chemokines in the CNS. These data propose LNC as an interesting drug delivery tool and TAT-coated PGD2-G-LNC remains a good candidate, in need of further work.
{"title":"Lipid nanocapsules for the nose-to-brain delivery of the anti-inflammatory bioactive lipid PGD2-G","authors":"Ariane Mwema M BBMC , Pauline Bottemanne PhD , Adrien Paquot M FARM , Bernard Ucakar Bachelor , Kevin Vanvarenberg Bachelor , Mireille Alhouayek PhD , Giulio G. Muccioli PhD , Anne des Rieux PhD","doi":"10.1016/j.nano.2022.102633","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102633","url":null,"abstract":"<div><p>Here, prostaglandin D<sub>2</sub>-glycerol ester (PGD<sub>2</sub>-G) was selected to target neuroinflammation. As PGD<sub>2</sub>-G is reported to have a short plasmatic half-life, we propose to use lipid nanocapsules (LNC) as vehicle to safely transport PGD<sub>2</sub>-G to the central nervous system (CNS). PGD<sub>2</sub>-G-loaded LNC (PGD<sub>2</sub>-G-LNC) reduced pro-inflammatory cytokine expression in activated microglial cells, even so after crossing a primary olfactory cell monolayer. A single nasal administration of PGD<sub>2</sub>-G-LNC in lipopolysaccharide (LPS)-treated mice reduced pro-inflammatory cytokine expression in the olfactory bulb. Coating LNC's surface with a cell-penetrating peptide, transactivator of transcription (TAT), increased its accumulation in the brain. Although TAT-coated PGD<sub>2</sub>-G-LNC modestly exerted its anti-inflammatory effect in a mouse model of multiple sclerosis similar to free PGD<sub>2</sub>-G after nasal administration, TAT-coated LNC surprisingly reduced the expression of pro-inflammatory chemokines in the CNS. These data propose LNC as an interesting drug delivery tool and TAT-coated PGD<sub>2</sub>-G-LNC remains a good candidate, in need of further work.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3457442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}