Polymer Chemistry
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2021
·Vol. 13
·期 7
·914-921
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IF 5.582
Fei Deng,Menglin Yang,Yanli Zhang,Xiaohui Wu,Rujiang Ma,Feihe Ma,Linqi Shi
Refolding a denatured protein into its native form and stabilizing its structure are significant in the production and storage of protein products. The self-assembled mixed-shell polymeric micelle (MSPM) based nanochaperones closely mimic natural molecular chaperones in terms of structure and function and have been widely used to regulate the (re)folding of denatured proteins. However, the traditional manufacturing method of MSPM based nanochaperones is inconvenient with a very low concentration, which greatly restricts its large-scale applicability in practice. Here, we developed a one-pot strategy to synthesize high-concentration MSPMs for the mass preparation of nanochaperones to refold bulk denatured proteins and stabilize the structure of native proteins. The high-concentration MSPM is synthesized using two macro-RAFT agents to induce the polymerization and cross-linking of hydrophobic monomers. Through this one pot synthesis method, MSPMs with a concentration of 36.8 mg ml−1 are obtained, which is much higher than that obtained through the traditional method (0.5 mg ml−1). Moreover, the obtained MSPMs provide a good renaturation efficiency for the refolding of bulk denatured proteins and can stabilize native proteins for long-term storage. This strategy provides a simple method for the mass preparation of functional nanochaperones, which will promote its applications in practice.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Yaxuan Zhao,Xuan Zhang,Min Sun,Ni An,Yuhuan Chen,Fang Yang
The poor water solubility of anticancer drugs significantly limits their therapeutic efficacy. Amphiphilic micelles with hydrophilic shells have emerged as promising anticancer drug carriers due to their remarkable ability to improve drug bioavailability. In this study, a Lysine-Arginine polyesteramide containing pendant carboxyl groups was synthesized (Lys-Arg-PEA). Subsequently, a series of amphiphilic comb-like copolymer micelle (AcDex-Lys-Arg-PEA) was developed through combination with acetylated dextran derivatives of different substitution degrees. The results revealed that the blank micelles maintained stable spherical structures with a uniform size distribution. The micellar system exhibited favorable hemocompatibility (hemolysis rate <5% and protein adsorption <30%), negligible cytotoxicity (cell viability >90% at 80 μg/mL concentration) and enzymatic degradability. Curcumin (Cur) was employed as a model drug to evaluate the anticancer drug delivery potential of this system. The micelles achieved high encapsulation efficiency (63%–85%) and drug loading capacity. Cur-loaded micelles showed significant inhibitory effects on HeLa cells (cell viability <55% at 80 μg/mL concentration). Drug release simulations in PBS buffer revealed pH-responsive characteristics, and the micelles exhibited faster Cur release at a cancerous pH (5.4, 50%–60%) than at a physiological pH (7.4, 30%–40%). This study demonstrates the potential of the comb-like copolymer micelles as effective carriers for anticancer drug delivery, providing valuable insights for subsequent research.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 6
Jing Liu,Jingxin Gou,Yanjiao Wang,Haibing He,Xing Tang
An enzyme/pH dual-responsive HES-10-HCPT prodrug micelle was developed. • The micelles achieved high drug loading (20%) and good stability. • Drug release was accelerated under acidic pH and enzymatic conditions. • HH-2 showed 42.5-fold lower IC50 than free 10-HCPT in 4T1 cells. • HH-2 achieved 52.22% tumor inhibition. Cancer remains a major global public health challenge, posing a substantial threat to human health and socioeconomic development. 10-hydroxycamptothecin (10-HCPT), a potent topoisomerase I inhibitor, exhibits broad antitumor activity; however, its clinical application is limited by poor aqueous solubility, rapid lactone-ring opening under physiological pH, and low bioavailability. To address these limitations, we developed an enzyme- and pH-dual-responsive polymer prodrug nanocarrier based on hydroxyethyl starch (HES). 10-HCPT was conjugated to the HES backbone through a hydrolysable succinate ester linkage, yielding an amphiphilic HES-10-HCPT prodrug capable of self-assembling into micelles. The resulting polymer prodrug micelles exhibited favorable storage and plasma stability. Importantly, drug release was accelerated under acidic and enzymatic conditions, suggesting tumor microenvironment-responsive release behavior. In vitro cytotoxicity assays against 4T1 breast cancer cells showed that the high-drug-loading micelles, HH-2, displayed markedly enhanced potency, with an IC50 value of 0.651 μg/mL, compared with free 10-HCPT, which showed an IC50 value of 27.7 μg/mL. In vivo studies in 4T1 tumor-bearing mice demonstrated that, at an equivalent 10-HCPT dose, HH-2 achieved a tumor inhibition rate of 46.31%, compared with 19.70% for free 10-HCPT. Histological analysis further suggested a favorable preliminary safety profile. Overall, this HES-based polymer prodrug micelle system provides a promising strategy for improving the stability, therapeutic efficacy, and safety of 10-HCPT and may serve as a potential platform for cancer chemotherapy. Download: Download high-res image (67KB) Download: Download full-size image
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FUEL
·
2023
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IF 7.4
Mingwei Gao,Mingshan Zhang,Peng Liu,Caili Dai,Qing You,Qiang Xue,Mingwei Zhao,Zhehui Jin
CO 2 enhanced oil recovery (CO 2 -EOR) is one of the CO 2 utilization methods which can also geo-sequestrate greenhouse gases. Due to the weak adsorption on rock surface and excellent viscoelasticity performance, CO 2 -responsive zwitterionic wormlike micelles (WLMs) has been recognized as a promising method to control CO 2 channeling. A novel CO 2 responsive zwitterionic WLMs was developed by blending N -octadecyl- N , N -dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate (OHSB), N , N , 2 , 2 -tetramethyl-1,3-propanediamine (TADPA) and sodium salicylate (NaSal). The responsive behaviors induced by varying agents (CO 2 and HCl) are systematically studied by rheology tests and cryo-TEM measurements. The molecular structures of products are confirmed by 1 H and 13 C NMR. Moreover, the responsive mechanism is discussed in detail. The OHSB/NaSal/TADPA system shows morphological transformations between spherical micelles (a good flowing capacity) and WLMs (conducive to plugging) before and after purging CO 2 . The viscoelasticity and molecular structure of the system with CO 2 bubbling is different from that with HCl titration, because TADPA molecules can react with CO 2 to form a novel zwitterionic product: NH + (CH 3 ) 2 -CH 2 -C(CH 3 ) 2 -CH 2 -NHCO 2 − (TAH + DPACO 2 − , 78.95 %–83.52 %). This work provides a new strategy for the design of CO 2 -responsive zwitterionic WLMs and their applications in CO 2 utilization schemes, including clean fracturing, mobility control, and CO 2 foam flooding, etc.
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Drug Delivery and Translational Research
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2023
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IF 5.4
Xiao Chuyao,Li Genyun,Li Xiaoyue,Wang Dan,Wu Ya,Sun Minghui,Huang Jiangeng,Si Luqin
Ulcerative colitis (UC) is an idiopathic, chronic, relapsing disease. In most cases, only the distal colon is affected, and the colonic stasis or fast colonic transit through the inflamed colon usually results in reduced exposure of the distal inflamed colon. Although the immunosuppressant cyclosporine A (CsA) has been used in patients with severe colitis who do not respond to corticosteroids, the clinical application of CsA remains limited due to the systemic toxicities and insufficient accumulation at the site of action for the intravenous and oral routes. In this study, we loaded CsA into the amphipathic poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles and then embedded them in hydrogels consisting of chitosan, poloxamer 188, and poloxamer 407 to construct a thermosensitive and mucoadhesive hydrogel drug delivery system (PLCP). The PLCP presented a high drug-loading capacity and showed a stable and rapid gelation rate after rectal administration into the body. Compared to CsA-loaded micelles and Sandimmun (Neoral ® ), the developed thermosensitive gel exhibited prolonged retention on the inflamed colon, as seen from in vitro adhesion and in vivo distribution experiments. It also fast mitigated colitis symptoms in TNBS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-1β, COX-2, and iNOS2), anti-inflammatory cytokines (IL-10, Nrf2, NQO1, and HO-1), and other relevant biochemical factors. Our results suggested that CsA-loaded micelle thermal hydrogel system could be a promising strategy by enhancing the retention in the diseased colon and promoting the relief and recovery of UC. Graphical Abstract
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International Journal of Nanomedicine
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2023
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IF 8
Yupeng Liu,Suhuan Dai,Lijuan Wen,Yun Zhu,Yanan Tan,Guoxi Qiu,Tingting Meng,Fangying Yu,Hong Yuan,Fuqiang Hu
Background Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis.Methods In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation.Results In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation.Conclusion The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2023
·Vol. 140
·期 44
·e54614
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IF 3
Yingxue Xu,Na Liang,Jia Fu,Zhe Zong,Xueling Long,Shaoping Sun
In this study, a polymer with tumor targeting function and dual redox/pH sensitivity is designed and synthesized by integrating chitosan (CS), Poloxamer 407 (P407), cholesterol (CHO), folic acid (FA), and disulfide bonds into one molecule (P407-CS(FA)-SS-CHO). The polymer can self-assemble in water to form micelles and solubilize paclitaxel (PTX). The mean particle size of PTX-loaded P407-CS(FA)-SS-CHO micelles is 133 nm. In vitro drug release study demonstrates the acid and glutathione (GSH) triggered PTX release behavior of the micelles. In vitro and in vivo experiments demonstrate the excellent tumor growth inhibition efficacy and low systemic toxicity of the PTX-loaded micelles. The P407-CS(FA)-SS-CHO micelles will be potential intelligent drug carriers for PTX delivery.
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ACS Applied Materials & Interfaces
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2023
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IF 9.5
Jiamin Chen,Xingxing Liu,Shujing Zhao,Hongyican Chen,Tao Lu,Jinfeng Wang,Jiahui Han,Wangran Wu,Xian Shen,Chao Li
Due to the intrinsic weak immunogenicity of tumor cells and the quantitatively and functionally different populations of immune cells, immunosuppression has become the major obstacle for cancer immunotherapy. In this study, the biocompatible alginate was chemically modified with the carboxyethyl linker to facilitate the esterification reaction of the resultant carboxymethylated alginate (CMA) and resiquimod (R848), the agonist of Toll-like receptor 7/8 (TLR7/8a). In aqueous solution, the hydrophilic CMA and the hydrophobic R848 formed stable nanomicelles (CMA-R848) by self-assembling. After combined administration of CMA-R848 and cisplatin (Cis) in a gastric cancer (GC) model, the long-circulating CMA-R848 micelle reached the mild acidic tumor microenvironment (TME); the ester bonds were quickly cleaved by the ubiquitous esterase and released the single molecule of R848. In vitro and in vivo results demonstrated that the released R848 efficiently promoted co-stimulatory molecules’ expression of dendritic cells (DCs), enhanced the antigen uptake and cross-presentation, and primed the cytotoxic T lymphocytes’ (CTLs) infiltration and killing effects, thereby reprogramming the “cold tumor” into the “hot tumor”. In addition, the ex vivo tumor sections revealed that the released R848 effectively repolarized the M2-like tumor-associated macrophages (TAMs) into M1-like macrophages, exerted synergistic antitumor activity, reduced the tumor burden, and prolonged the overall survival duration of the GC animal model. Our study provided a targeting therapeutic strategy overcoming the limitations of R848 in vivo, and enhanced the efficacy of GC chemotherapy and immunotherapy by TME modulation.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/ [email protected] ) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/ [email protected] are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4 + /CD8 + T cells by silencing PD-L1 expression. In vivo studies show that R/C/ [email protected] exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
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Acta Biomaterialia
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2022
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IF 10.633
Liyue Zhou,Qiangwei Liang,Yifan Li,Yongjing Cao,Juan Li,Jiayu Yang,Jinxia Liu,Jiawei Bi,Yanhua Liu
Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo , CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization . Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. Statement of significance A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.
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INDUSTRIAL CROPS AND PRODUCTS
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2023
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IF 5.9
Pengfei Shan,Ming Zhang,Xiaoyue Lian,Weilin Lu,Xiangping Yin,Haiwei Liu,Yingwen Lu,Qi Yuxi,Jiabin Jiang,Zhihui Li,Zhongyu Li
The low utilization efficacy of conventional herbicide formulations greatly harms the environment and human health. Inspired by the fact that many drug delivery systems are designed to achieve targeted release triggered by the microenvironment of tumor tissues in cancer therapy, a tartaric acid-derived polyester with hydrophilic acid-degradable side chains was designed and synthesized for site-specific herbicide delivery by utilizing the acidic microenvironment in the rhizosphere . The amphiphilic polymer can spontaneously form polymeric micelles in the aqueous solution to load diuron. The diuron-loaded polymeric micelles can release diuron under acidic conditions, and the release rate increase with the reduction of pH value. The herbicidal effect of the diuron-loaded polymeric micelles is investigated using barnyard grass as the research object. The results reveal that the diuron-loaded polymeric micelles are able to kill barnyard grass effectively. Finally, the toxicity studies suggest that the polymer can mitigate toxicity to the non-target organisms. In view of its superior herbicidal activity, excellent biodegradability and biocompatibility, this site-specific herbicides release system has broad potential in agricultural applications.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Kehong Dong,Yuxuan Sun,Xintao Gao,Jing Wang,Xiaochen Wu,Chuanlong Guo
Excessive acetaminophen (APAP) is the main cause of drug-induced acute liver failure, and the pathogenesis has not been elucidated and there is a lack of effective drugs. Hesperidin (Hes), a rich flavanone in citrus peel with excellent biological activities, is a potential agent for treatment liver injury. Due to poor water solubility of Hes, this study prepared mixed micelles using polyvinyl pyrrolidone (PVP K17) and poloxamer 188, and encapsulated Hes (Hes-MMs). The results showed that Hes-MMs exhibited a uniform spherical shape with a particle size of 66.80 ± 0.83 nm, and Hes-MMs significantly improved the dispersibility, antioxidant activity , and cellular uptake of Hes. In vitro results showed that Hes-MMs protected the proliferation inhibition of HepG2 cells induced by APAP, inhibited the production of reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP) induced by APAP. Furthermore, Hes-MMs exerted liver protective effects by inhibiting APAP induced mtDNA release and activating the cGAS-STING pathway. In vivo results demonstrated that Hes-MMs showed protective and therapeutic effects on APAP induced liver injury, and their mechanisms were related to the mtDNA-cGAS-STING signaling pathway . In summary, our study demonstrated that the mtDNA-cGAS-STING pathway was involved in APAP induced acute liver injury, and Hes-MMs might be a potential therapeutic agent for treating APAP induced acute liver injury.
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