JOURNAL OF BIOTECHNOLOGY
·
2025
·
IF 3.9
Xin Liu,Mengqiu Sun,Lu Dai,Yusheng Li,Rui Song,Hong Bian,Hao Zhang
Combination chemotherapy presents a promising approach to overcome multidrug resistance in cancer treatment. However, conventional delivery systems struggle to achieve synchronized co-delivery of hydrophilic and hydrophobic therapeutics with tumor-specific targeting and controlled release. Here, we developed a multifunctional nanocarrier integrating poly (lactic-co-glycolic acid) nanoparticles with polydopamine and programmable nucleic acids. Within this system, the hydrophobic core encapsulates lipophilic drugs, while the surface nucleic acid architecture enables hydrophilic drug loading via molecular intercalation. Furthermore, tumor-targeting aptamers guide selective cellular uptake, and a tumor microenvironment-responsive mechanism ensures spatiotemporally controlled drug release. As demonstrated experimentally, this unified platform demonstrates promising antitumor activity with potential advantages in drug delivery efficiency. By combining targeted delivery, differential drug loading, and stimuli-triggered release, the design establishes a modular framework for precision combination therapies, thereby advancing adaptable nanomedicine in oncology.
研究领域:
肿瘤学
·
生物医学工程
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2021
·Vol. 13
·期 9
·1515
·
IF 4.329
Xiukun Xue,Yanjuan Wu,Xiao Xu,Ben Xu,Zhaowei Chen,Tianduo Li
Polymeric prodrugs, synthesized by conjugating chemotherapeutic agents to functional polymers, have been extensively investigated and employed for safer and more efficacious cancer therapy. By rational design, a pH and reduction dual-sensitive dextran-di-drugs conjugate (oDex-g-Pt+DOX) was synthesized by the covalent conjugation of Pt (IV) prodrug and doxorubicin (DOX) to an oxidized dextran (oDex). Pt (IV) prodrug and DOX were linked by the versatile efficient esterification reactions and Schiff base reaction, respectively. oDex-g-Pt+DOX could self-assemble into nanoparticles with an average diameter at around 180 nm. The acidic and reductive (GSH) environment induced degradation and drug release behavior of the resulting nanoparticles (oDex-g-Pt+DOX NPs) were systematically investigated by optical experiment, DLS analysis, TEM measurement, and in vitro drugs release experiment. Effective cellular uptake of the oDex-g-Pt+DOX NPs was identified by the human cervical carcinoma HeLa cells via confocal laser scanning microscopy. Furthermore, oDex-g-Pt+DOX NPs displayed a comparable antiproliferative activity than the simple combination of free cisplatin and DOX (Cis+DOX) as the extension of time. More importantly, oDex-g-Pt+DOX NPs exhibited remarkable reversal ability of tumor resistance compared to the cisplatin in cisplatin-resistant lung carcinoma A549 cells. Take advantage of the acidic and reductive microenvironment of tumors, this smart polymer-dual-drugs conjugate could serve as a promising and effective nanomedicine for combination chemotherapy.Keywords:polymeric prodrug;dual-sensitive;combination chemotherapy;drug conjugation;dextran
研究领域:
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2015
·
IF 4.513
Minxi Hu,Ping Huang,Yao Wang,Yue Su,Linzhu Zhou,Xinyuan Zhu,Deyue Yan
Combination chemotherapy has been widely applied in cancer treatment; however, the cocktail administration of combination chemotherapy could cause the nonuniform biodistribution of anticancer agents, thus impairing the therapeutic efficacy. In the present study, to address this concern, we proposed a novel strategy of preparing self-assembled nanoparticles from amphiphilic drug–drug conjugate for synergistic combination chemotherapy. The conjugate was synthesized by two-step esterification of hydrophobic camptothecin (CPT) and hydrophilic floxuridine (FUDR) through a linker compound. Because of its amphiphilic nature, the CPT-FUDR conjugate self-assembled into stable nanoparticles which could simultaneously release fixed dosage of the two drugs in cancer cells. In vitro studies demonstrated synergistic anticancer efficacy of the CPT-FUDR nanoparticles including improved cell apoptosis, varied cell cycle arrest, as well as effective inhibition of cancer cell proliferation.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2010
·
IF 7.365
Hongbin Zhang,Chen Zhao,Hui Cao,Guojie Wang,Li Song,Guoguang Niu,Huai Yang,Jie Ma,Siquan Zhu
Combination chemotherapy has been a primary management for cancer. Thus a drug delivery system which can administer several drugs simultaneously and control the drug release at the cancer site is desired. Here we synthesized hyperbranched poly(amine-ester) (HPAE) macromers with different degrees of terminal C C modification to make injectable hydrogels as a multi-drug delivery system. The aqueous solutions of the macromers were fast transformed into hydrogel at body temperature with a low concentration (0.05 wt%) of ammonium persulfate (APS) but no activator for accelerating the polymerization, since the HPAE macromer with tertiary amines and APS themselves formed a redox system as initiator. Three different types of drugs, doxorubicin hydrochloride (Dox), 5-fluorouracil (5FU) and leucovorin calcium (LC), were used as model drugs in this experiment. This system allows locally releasing single and/or combinations of anticancer drugs simultaneously by a controllable way. Behaviors of drug release can be controlled by the drug-loading methods or/and the C C modification degree of macromers loaded with the drug molecules. The drug release period could be prolonged when the drug was loaded into the macromers with high content of C C. The HPAE macromers exhibited good biocompatibility which was evaluated in L929 and MCF7 cell lines using MTT cell proliferation assay. The swelling behavior and degradation of HPAE hydrogels in vitro were also examined. These results suggest that the HPAE hydrogels hold great potential for use as injectable systems for locally delivering single and/or multiple drugs in chemotherapy of cancer.
研究领域:
生物材料学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 2
·332-342
·
IF 5.047
Huihui Shi,Ming Xu,Jianhua Zhu,Yang Li,Zhiyu He,Yuxia Zhang,Qunwei Xu,Yimin Niu,Yang Liu
Recently, ultra-small platinum nanoparticles (USPtNs) have been found that can kill cancer cells by leaching Pt ions into acidic organelles, such as cell endosomes or lysosomes. Unfortunately, tumor-specific accumulation is difficult to achieve with such platinum nanodrugs of less than 5 nm due to their short half-life in vivo and broad range of toxicity to normal tissues. Programmable multi-drug release for combinational chemotherapy by hierarchical nanostructures provides a promising solution for cancer-targeted therapy. Herein, we demonstrated a pH/redox dual stimuli-responsive clustered nanoparticle as a vehicle for simultaneously delivering USPtNs and gemcitabine (GEM) to treat non-small-cell lung cancer. The clustered nanoparticle (denoted as GP-NA) was composed of disulfide-bond-containing GEM-grafted copolymers (PEG-b-P(LL-g-GEM)), pH-sensitive polypeptides (OAPI), and USPtNs. Such a hybrid nanosystem completes multiple tasks inside cancer cells, which include the generation of cytotoxic Pt ions in response to lysosomal acidic environments and the subsequent release of GEM in cytoplasmic reduction environments. Compared with non-acid-sensitive nanoparticles or free drugs, GP-NA exhibited cumulative and enhanced anti-tumor efficacy in vivo, which may be attributed to the simultaneous inhibition of ribonucleotide reductase and DNA replication in nuclei by the GEM and Pt ions. Together, our work provides a promising strategy in the co-delivery of USPtNs and GEM for precision cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS TECHNOLOGY
·
2015
·
IF 1.227
H. Wu,J. Peng,S. Wang,B. Xie,L. Lei,D. Zhao,H. Nie
Controlled delivery of dual chemical drugs may increase the efficiency of chemotherapy. In this work, doxorubicin (DOX) was bound to adamantanecarboxylic acid (AD-COOH) through covalent linkage to form AD-DOX, while graphene oxide (GO) was modified by ethylenediamino-β-cyclodextrin (EDA-CD) to form graphene oxide-β-cyclodextrin (GO-CD), then GO-CD was assembled with as-produced AD-DOX via host–guest interaction. In contrast to the conjugation of DOX via covalent linkage, topotecan (TPT) was loaded onto GO through π–π stacking interaction. It was found that TPT/GO-CD/AD-DOX nanoparticles synchronised the delivery of DOX and TPT, and pH value played a critical role in determining the release profiles of dual drugs. Moreover, in vitro cellular investigations proved that TPT/GO-CD/AD-DOX nanoparticles were superior to free drugs and single-drug loaded nanoparticles in inhibiting the growth of HeLa cells. As a kind of injectable biomaterials, this controlled drug delivery device offers a solution to simultaneous delivery of dual chemical drugs in cancer lesion positions. Authors expect that this platform can be exploited for controlled delivery of various drug combinations for combination chemotherapy.
研究领域:
纳米医学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2018
·
IF 4.56
Lingfei Han,Lejian Hu,Fulei Liu,Xin Wang,Xiaoxian Huang,Bowen Liu,Feng Feng,Wenyuan Liu,Wei Qu
The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) – all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore, redox-sensitive HA-SS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Shaodong Zhai,Xianglong Hu,Yongjun Hu,Baoyan Wu,Da Xing
Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine . Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG- b -PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments . In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 11
·5765-5779
·
IF 7.79
Yamei Huang,Dengchao Xie,Shuangquan Gou,Brandon S. B. Canup,Guizheng Zhang,Fangyin Dai,Changming Li,Bo Xiao
The synergism of combination chemotherapy can only be achieved under specific drug ratios. Herein, hyaluronic acid (HA)-functionalized regenerated silk fibroin-based nanoparticles (NPs) were used to concurrently deliver curcumin (CUR) and 5-fluorouracil (5-FU) at various weight ratios (3.3 : 1, 1.6 : 1, 1.1 : 1, 1 : 1, and 1 : 1.2) to breast tumor cells. The generated HA-CUR/5-FU-NPs were found to have desirable particle sizes (around 200 nm), narrow size distributions, and negative zeta potentials (about −26.0 mV). Interestingly, these NPs showed accelerated drug release rates when they were exposed to buffers that mimicked the multi-hallmarks in the tumor microenvironment (pH/hydrogen peroxide/glutathione/hyaluronidase). The surface functionalization of NPs with HA endowed them with in vitro and in vivo breast tumor-targeting properties. Furthermore, we found that the co-loading of CUR and 5-FU in HA-functionalized NPs exhibited obvious synergistic anti-cancer, pro-apoptotic, and anti-migration effects, and the strongest synergism was found at the CUR/5-FU weight ratio of 1 : 1.2. Most importantly, mice experiments revealed that HA-CUR/5-FU-NPs (1 : 1.2) showed a superior anti-cancer activity against metastatic breast cancer compared to the single drug-loaded NPs and non-functionalized CUR/5-FU-NPs (1 : 1.2). Collectively, these results demonstrate that HA-CUR/5-FU-NPs (1 : 1.2) can be exploited as a robust nanococktail for the treatment of breast cancer and its lung metastasis.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）