Zozan Guleken PhD , Zeynep Ceylan PhD , Aynur Aday PhD , Ayşe Gül Bayrak PhD , İpek Yönal Hindilerden MD, Prof. , Meliha Nalçacı MD, Prof. , Paweł Jakubczyk Prof. , Dorota Jakubczyk PhD , Monika Kula-Maximenko PhD , Joanna Depciuch PhD
{"title":"Detection of primary myelofibrosis in blood serum via Raman spectroscopy assisted by machine learning approaches; correlation with clinical diagnosis","authors":"Zozan Guleken PhD , Zeynep Ceylan PhD , Aynur Aday PhD , Ayşe Gül Bayrak PhD , İpek Yönal Hindilerden MD, Prof. , Meliha Nalçacı MD, Prof. , Paweł Jakubczyk Prof. , Dorota Jakubczyk PhD , Monika Kula-Maximenko PhD , Joanna Depciuch PhD","doi":"10.1016/j.nano.2023.102706","DOIUrl":"10.1016/j.nano.2023.102706","url":null,"abstract":"<div><p><span><span><span>Primary myelofibrosis<span> (PM) is one of the myeloproliferative neoplasm, where stem cell-derived clonal neoplasms was noticed. Diagnosis of this disease is based on: physical examination, peripheral blood findings, bone marrow morphology, cytogenetics, and </span></span>molecular markers<span><span>. However, the molecular marker of PM, which is a mutation in the JAK2V617F gene, was observed also in other myeloproliferative neoplasms such as polycythemia vera<span> and essential thrombocythemia. Therefore, there is a need to find methods that provide a marker unique to PM and allow for higher accuracy of PM diagnosis and consequently the </span></span>treatment<span><span><span> of the disease. Continuing, in this study, we used Raman spectroscopy, </span>Principal Components Analysis<span> (PCA), and Partial Least Squares (PLS) analysis as helpful diagnostic tools for PM. Consequently, we used serum collected from PM patients, which were classified using clinical parameters of PM such as the dynamic </span></span>international prognostic scoring system<span><span> (DIPSS) for primary myelofibrosis plus score, the JAK2V617F mutation, spleen size, bone marrow </span>reticulin<span> fibrosis degree and use of </span></span></span></span></span>hydroxyurea<span><span> drug features. </span>Raman spectra showed higher amounts of C-H, C-C and C-C/C-N and amide II and lower amounts of amide I and vibrations of CH</span></span><sub>3</sub><span> groups in PM patients than in healthy ones. Furthermore, shifts of amides<span> II and I vibrations in PM patients were noticed. Machine learning methods were used to analyze Raman regions: (i) 800 cm</span></span><sup>−1</sup> and 1800 cm<sup>−1</sup>, (ii) 1600 cm<sup>−1</sup>–1700 cm<sup>−1</sup>, and (iii) 2700 cm<sup>−1</sup>–3000 cm<sup>−1</sup><span> showed 100 % accuracy, sensitivity, and specificity. Differences in the spectral dynamic showed that differences in the amide II and amide I regions were the most significant in distinguishing between PM and healthy subjects. Importantly, until now, the efficacy of Raman spectroscopy has not been established in clinical diagnostics of PM disease using the correlation between Raman spectra and PM clinical prognostic scoring. Continuing, our results showed the correlation between Raman signals and bone marrow fibrosis, as well as JAKV617F. Consequently, the results revealed that Raman spectroscopy has a high potential for use in medical laboratory diagnostics to quantify multiple biomarkers simultaneously, especially in the selected Raman regions.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10522993","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}
Clara Manesco MSc , Oscar Saavedra-Villanueva PhD , Marta Martin PhD , Joshua de Lizaraga MSc , Béla Varga PhD , Thierry Cloitre PhD , Yannick Nicolas Gerber PhD , Florence Evelyne Perrin Prof. , Csilla Gergely Prof.
{"title":"Organization of collagen fibers and tissue hardening: Markers of fibrotic scarring after spinal cord injury in mice revealed by multiphoton-atomic force microscopy imaging","authors":"Clara Manesco MSc , Oscar Saavedra-Villanueva PhD , Marta Martin PhD , Joshua de Lizaraga MSc , Béla Varga PhD , Thierry Cloitre PhD , Yannick Nicolas Gerber PhD , Florence Evelyne Perrin Prof. , Csilla Gergely Prof.","doi":"10.1016/j.nano.2023.102699","DOIUrl":"10.1016/j.nano.2023.102699","url":null,"abstract":"<div><p><span><span>Spinal cord injury is a dramatic disease leading to severe motor, sensitive and </span>autonomic<span><span> impairments. After injury the axonal regeneration is partly inhibited by the </span>glial scar, acting as a physical and chemical barrier. The scarring process involves </span></span>microglia<span><span><span>, astrocytes and extracellular matrix components, such as collagen, constructing the fibrotic component of the scar. To investigate the role of collagen, we used a multimodal label-free imaging approach combining multiphoton and </span>atomic force microscopy<span>. The second harmonic generation signal exhibited by </span></span>fibrillar collagen enabled to specifically monitor it as a biomarker of the lesion. An increase in collagen density and the formation of more tortuous fibers over time after injury are observed. Nano-mechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers' formation. These observations indicate the concomitance of important structural and mechanical modifications during the fibrotic scar evolution.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064900","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}
Troy A. Halseth PhD , Adele B. Correia BS , Mark L. Schultz PhD , Maria V. Fawaz PhD , Esmée Q. Kuiper BS , Preethi Kumaran BS , Kristen Hong Dorsey MS , Edward H. Schuchman PhD , Andrew P. Lieberman MD,PhD , Anna Schwendeman PhD
{"title":"Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency","authors":"Troy A. Halseth PhD , Adele B. Correia BS , Mark L. Schultz PhD , Maria V. Fawaz PhD , Esmée Q. Kuiper BS , Preethi Kumaran BS , Kristen Hong Dorsey MS , Edward H. Schuchman PhD , Andrew P. Lieberman MD,PhD , Anna Schwendeman PhD","doi":"10.1016/j.nano.2023.102705","DOIUrl":"10.1016/j.nano.2023.102705","url":null,"abstract":"<div><p><span><span>Acid sphingomyelinase deficiency (ASMD) is a severe </span>lipid<span> storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of </span></span>sphingomyelin<span> in late endosomes and lysosomes<span><span> leading to progressive neurological dysfunction and hepatosplenomegaly<span>. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the </span></span>treatment<span><span> of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts<span> in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) </span></span>nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD.</span></span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145234","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}
Sylwia Michlewska PhD , Dagmara Wójkowska PhD , Cezary Watala Professor , Elżbieta Skiba PhD , Paula Ortega Professor , Francisco Javier de la Mata Professor , Maria Bryszewska Professor , Maksim Ionov Professor
{"title":"Ruthenium metallodendrimer against triple-negative breast cancer in mice","authors":"Sylwia Michlewska PhD , Dagmara Wójkowska PhD , Cezary Watala Professor , Elżbieta Skiba PhD , Paula Ortega Professor , Francisco Javier de la Mata Professor , Maria Bryszewska Professor , Maksim Ionov Professor","doi":"10.1016/j.nano.2023.102703","DOIUrl":"10.1016/j.nano.2023.102703","url":null,"abstract":"<div><p>Carbosilane metallodendrimers, based on the arene Ru(II) complex (<strong>CRD13</strong>) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. <em>In vivo</em> investigations proved that a local injection of <strong>CRD13</strong> caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000540/pdfft?md5=910f44dfd820b4b18cc03e60680c80ec&pid=1-s2.0-S1549963423000540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10081397","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}
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
{"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":null,"pages":null},"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}
{"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":null,"pages":null},"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}
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
{"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":null,"pages":null},"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
{"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":null,"pages":null},"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
{"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":null,"pages":null},"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
{"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":null,"pages":null},"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}