Biomaterials Science
·
2019
·Vol. 7
·期 8
·3277-3286
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IF 5.251
Jun Li,Zu-E. Hu,Xian-Ling Yang,Wan-Xia Wu,Xiu Xing,Bo Gu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Dual stimuli-responsive camptothecin polymeric prodrugs (CPT Prodrugs) with grafted structures were designed via chemoenzymatic methods and combined with doxorubicin (DOX) for synergistic drug delivery to improve anticancer efficiency. The CPT Prodrugs loaded DOX with a high efficiency through the cooperative contribution of several interaction forces. The produced amphiphilic polymeric prodrugs loaded with DOX, referred to as DOX@CPT Prodrugs, formed homogeneous spherical micelles of appropriate sizes (sub-50 nm). The DOX@CPT Prodrug micelles showed excellent stability in release experiments under in vitro physiological conditions and maintained over 80% drug loading after 4 weeks when stored at 4 °C. Under weakly acidic pH and reduced glutathione (GSH) conditions, the DOX@CPT Prodrugs with high disulfide and tertiary amine content achieved synergistic release of the two loaded drugs and biodegraded into low-molecular-weight compounds. The cell experiments confirmed that the internalization of DOX@CPT Prodrugs into cancer cells was greatly improved by nearly 30% compared with that of free drugs. Furthermore, the synergistic drug delivery system exhibited superior anticancer efficiency with highly improved cell selectivity ratios (up to 127.0%) and greatly enhanced synergistic effects (up to 23.9%) benefiting from good long-term stability, better internalization by cells and sensitive pH and GSH dual-responsivity. In addition, the DOX@CPT Prodrugs with suitable sizes and good water solubility also exhibited a greater penetrability in the case of simulating solid tumors than the free drugs. These results demonstrate the potential of DOX@CPT Prodrugs as biodegradable, dual-responsive combination therapy nanocarriers for synergistic anticancer treatment.
研究领域:
药学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Benkai Qin,Lei Liu,Xiaohe Wu,Fengguang Liang,Tian Hou,Yangyang Pan,Shiyong Song
We prepared an amphiphilic redox-responsive conjugate based on mPEGylated solanesol, solanesyl poly(ethylene glycol) dithiodipropionate (SPDP), along with its inert counterpart solanesyl poly(ethylene glycol) succinate (SPGS), which self-assembled in aqueous solution to form redox-responsive micelles . Used as efficient drug carriers for doxorubicin (DOX), the micelles acted as synergistic agents for cancer therapy. Dynamic light scattering (DLS) measurements showed that the SPDP micelles had average diameters of 111 nm, which decreased to 88 nm after the encapsulation of DOX. The mean diameters and size distribution of the disulfide-containing micelles changed obviously in the presence of the reducing agent glutathione (GSH), whereas no changes occurred in the case of redox-insensitive SPGS micelles. DOX could be loaded into both types of micelles, with drug loading content of about 4.0%. A significantly accelerated release of DOX was triggered by GSH for DOX-loaded SPDP micelles, compared with DOX-loaded SPGS micelles. Blank SPGS and SPDP micelles displayed higher inhibition of HeLa and MCF-7 cell proliferation but less cytotoxicity to normal L-02 cells at similar concentrations. Confocal microscopic observation indicated that a greater amount of DOX was delivered into the nuclei of cells following 9 or 12 h incubation with DOX-loaded micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded SPDP micelles over free DOX and DOX-loaded SPGS micelles. All of the data presented here suggested that these SPDP micelles may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs. Statement of Significance Various nanoscale drug carriers were used to enhance therapeutic effect of many drugs. While, the metabolites of high quantities of carriers may cause additional short- or long-term toxicities. In this study, a new systems based on solanesol derivatives was developed for anticancer drug delivery. There are two features for this system. One is solanesol originated bioactivity of the carrier, which will synergistically facilitate therapeutic effect of the encapsulated drug. The other is the redox-responsive drug release behavior adaptable to the glutathione-rich atmosphere of tumor cell. All the hypothesis have been elucidated in this work through in vitro and in vivo studies. It was found that this drug delivery system may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs.
研究领域:
药剂学
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肿瘤学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Longbing Ling,Muhammad Ismail,Zhihao Shang,Yihui Hu,Benhong Li
Irinotecan (Ir) is a potent antitumor chemotherapeutics in clinic and used for the treatment of a various cancers, but the degree of its application is critically limited by toxic side-effects and marked heterogeneities. Nano-formulation of prodrugs, based on “all-in-one” carrier-free self-assemblies offers an effective approach to alter pharmacokinetics and safety profiles of cytotoxic agents. In this study, a novel vitamin E succinate-based formulation of Ir (VES-Ir) combined with nanoscaled characteristics and synergistic combination was constructed through esterification. The conjugation makes amphiphilic VES-Ir prodrug self-assemble into nanoparticles with a fine diameter (VES-Ir NPs, 75.4 nm) of spherical morphology. Furthermore, VES-Ir NPs with a 1:1 drug-to-drug ratio was demonstrated to possess respectable physiological stability within 72 h test, while can react to pH/esterase-sensitive drug release in lysosomes internalized into tumor cells, potentially highlighting their alleviating side effects. Compared with single and mixture drugs administration, the nanoformulated VES-Ir NPs codelivered both VES and Ir with different anticancer mechanisms to induce the highest suppress proliferation of MCF-7 (IC 50 0.18 μM) and A549 (IC 50 0.29 μM) cells in a synergistic way (CI < 1). More importantly, the formulating nanoparticulate Ir is to significantly enhance its bioavailability in vivo with long retention time in bloodstream and thereby, resulting the superior tumor inhibitory rate (TIR) of 85.2% versus controls. This simple nanoformulation of Ir drug deprived from VES conjugation, together with self-delivery and synergistic property, may provide an effective strategy for multiple chemotherapeutics delivery to treat cancers or other diseases.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2017
·
IF 1.194
Wei Wang,Biyun Zhao,Xiangyang Meng,Pan She,Pantian Zhang,Yi Cao,Xuefei Zhang
The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer , named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs , i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1 H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.
研究领域:
药学
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肿瘤学
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纳米医学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yudian Qiu,Jie Bai,Yecheng Feng,Xiaojing Shi,Xubo Zhao
Synergistic therapy holds promising potential in cancer treatment. Here, the inclusion of catechol moieties, a disulfide cross-linked structure, and pendent carboxyl into the network of polymeric nanogels with glutathione (GSH)-responsive dissociation and pH-sensitive release is first disclosed for the codelivery of doxorubicin (DOX) and bortezomib (BTZ) in synergistic cancer therapy. The pendent carboxyl groups and catechol moieties are exploited to absorb DOX through electrostatic interaction and conjugate BTZ through boronate ester, respectively. Both electrostatic interactions and boronate ester are stable at neutral or alkaline pH, while they are instable in an acidic environment to further recover the activities of BTZ and DOX. The polymeric nanogels possess a superior stability to prevent the premature leakage of drugs in a physiological environment, while their structure is destroyed in response to a typical endogenous stimulus (GSH) to unload drugs. The dissociation of the drug-loaded nanogels accelerates the intracellular release of DOX and BTZ and further enhances the therapeutic efficacy. In vitro and in vivo investigations revealed that the dual-drug loaded polymeric nanogels exhibited a strong ability to suppress tumor growth. This study thus proposes a new perspective on the production of multifunctional polymeric nanogels through the introduction of different functional monomers.
研究领域:
生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTENGCOMM
·
2020
·Vol. 22
·期 45
·7992-8006
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IF 3.117
Yue-Ming Yu,Ling-Yang Wang,Fan-Zhi Bu,Lin-Lin Wang,Yan-Tuan Li,Cheng Wang,Zhi-Yong Wu
In order to give full play to the superiority of cocrystallization techniques to overcome biopharmaceutical limitations in vitro and ameliorate pharmacokinetic properties in vivo together with heightening the antitumor abilities of the anticancer drug 5-fluorouracil (FL), and to gain some further insights into the development of novel pharmaceutical cocrystals with synergetic antitumor activity between an active pharmaceutical ingredient and the former cocrystal, a new cocrystal of FL with caffeic acid (CF), namely FL-CF-2H2O, has been successfully exploited and systematically studied. Single-crystal X-ray diffraction analysis confirms that the asymmetric unit of the newly synthesized cocrystal consists of one FL, one CF and two solvent water molecules, in which the two complementary FL and CF molecules compose a planar hydrogen-bonding pair. Water molecules fill in the hole surrounded by three arrays of the pairs and link each other via hydrogen bonds to form a three-dimensional supramolecular network, which is further reinforced by aromatic packing interactions. The cocrystal characteristics in vitro and in vivo are systematically evaluated through a combination of theoretical and experimental methods. It is found that the permeability and solubility of FL from the FL-CF-2H2O cocrystal are synchronously enhanced relative to pure FL, which is supported by molecular electrostatic potential calculation and Hirshfeld surface analysis. Interestingly, the ameliorated in vitro biopharmaceutical characteristics can efficaciously change the in vivo optimized pharmacokinetics with prolonged half-life and increased bioavailability compared with FL itself. What is even more interesting is that CF and FL in the cocrystal exhibit synergistic antitumor effects on tested cell lines. Thus, this work not only provides a new crystalline form for FL with potential application prospects, but also initiates an intelligent idea for the development of synergistic antitumor pharmaceutical cocrystals.
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
DALTON TRANSACTIONS
·
2022
·Vol. 51
·期 17
·6846-6854
·
IF 4.569
Hongdong Shi,Simin Lin,Yi Wang,Jingxue Lou,Yatao Hu,Yuyu Chen,Qianling Zhang
Ruthenium polypyridyl complexes have been widely used as bioprobes and photosensitizers. However, several disadvantages including slow cellular uptake, nonspecific binding with biomolecules and toxicity limit their applications. In this study, a nanocarrier of human serum albumin coated gold nanorods was developed to deliver a ruthenium photosensitizer for PDT/PTT combination therapy. The HSA coating endowed the nanodrug with high biocompatibility and stability under physiological conditions. Ru-GNR-HSANPs generate 1O2 and hydroxyl radicals to kill cancer cells under blue light irradiation, and exhibit excellent photothermal anticancer effects under 808 nm light irradiation. Significant synergistic anticancer effects were achieved by combined PDT/PTT therapy. Importantly, Ru-GNR-HSANPs can have the synergistic PDT/PTT functions with no need of drug release from the carrier.
研究领域:
纳米医学
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肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Zaixiang Fang,Ling Lin,Zhiqian Li,Lei Gu,Dayi Pan,Yunkun Li,Jie Chen,Haitao Ding,Xiaohe Tian,Qiyong Gong,Kui Luo
The combination of chemotherapy and photodynamic therapy (PDT) has the potential to complement single-drug therapies, but chemotherapeutic agents and photosensitizers often have compromised therapeutic efficacies and strong toxic effects. In this study, we exploited nanotechnology to address this challenge by utilizing heparin as a carrier for co-delivery of chemotherapeutic drugs and photosensitizers for synergistic cancer therapy. Specifically, heparin-paclitaxel (HP-PTX) and heparin-pyropheophorbide-a (HP-Ppa) were synthesized by attaching paclitaxel (PTX), a small molecular chemotherapeutic drug, through a reactive oxygen species (ROS)-responsive linker and Ppa, a photosensitizer, to heparin, respectively. Two conjugates were co-assembled into a nanomedicine , HP-PP nanoparticles (NPs), for controllable co-delivery of Ppa and PTX into tumor cells. HP-PP NPs significantly enhanced the in vitro stability of HP-Ppa and the photostability of Ppa, and the synergistic actions of chemotherapy and PDT were confirmed by both in vitro and in vivo antitumor studies. Notably, HP-PP NPs enhanced tumor accumulation of Ppa up to 11-fold and the treatment of 4T1 tumor-bearing mice with HP-PP NPs resulted in a tumor growth inhibition of 98.1% without systemic toxicity. The strategy of co-assembly of heparin conjugates may offer great potential in enhancing the efficacy of combination therapy. Statement of significance We proposed a nano-delivery system, HP-PP NPs, which was constructed by co-assembly of heparin-paclitaxel (HP-PTX) and heparin-pyropheophorbide-a (HP-Ppa), to co-deliver PTX and Ppa for synergistic cancer therapy. HP-PP NPs enhanced the photostability and the in vitro stability of Ppa and HP-Ppa, and induced greater cytotoxicity than HP-PTX NPs or HP-Ppa NPs. This co-delivery system displays enhanced tumor accumulation and has a remarkable synergistic antitumor effect with a tumor growth inhibition of 98.1%.
研究领域:
药学
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肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Jiaojiao Li,Qing Du,Jiangling Wan,Deng-Guang Yu,Fei Tan,Xiangliang Yang
A tri-fluid electrospinning process was successfully developed to prepare tri-chamber complex nanofibers. The core–shell and Janus structure were combined to form a delicate and complicated architecture for solving the problem of co-administration of quercetin and tamoxifen citrate, improving the oral bioavailability, and enhancing their synergistic anti-breast cancer actions. Scanning electron microscope, transmission electron microscope and confocal fluorescent microscopy images showed the complex structure of the designed nanofibers. Fourier transform infrared and X-ray diffraction analyses verified that the model drugs and the polymeric excipients had good compatibility and were presented in an amorphous state. The in vitro release study certified that the tri-chamber nanofibers facilitated the rapid release of quercetin compared with that of the crude drug (90% versus 38%) and the delayed and sustained release of tamoxifen citrate at the same time interval (decreased by 1.88 times). The in vivo pharmacokinetic and pharmacodynamic analysis verified that the tri-chamber nanofibers could result in increased oral bioavailability and enhanced synergistic anticancer action of quercetin and tamoxifen citrate. The findings proved that a new medicated drug delivery system with advanced dual-, time-, and target-specific drug release profiles was developed using the electrospun complex nanostructure.
研究领域:
药剂学
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肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Li Wang,Mengzhen Yang,Ruijing Gao,Yu Pang,Xiaoshu Zhao,Guoqiang Zhou,Shutao Gao,Kun Ge,Jinchao Zhang
The nano-based therapeutics to induce cellular oxidative damage is considered promising in cancer treatment. Photodynamic therapy (PDT) is a primary antitumor oxidative damage treatment method. However, the hypoxic environment of tumor tissues and the short lifetime of singlet oxygen significantly hampers PDT efficacy. Fortunately, nitric oxide (NO), as a form of gas therapy, can generate more toxic oxidative peroxynitrite ions (ONOO − ) with hydrogen peroxide (H 2 O 2 ), which significantly enhance the efficacy of PDT. In this context, we fabricated a thermally controlled reactive oxygen nanobombs CaO 2 @LA-ICG@TD (CAI@TD), which can release many reactive oxygen species (ROS) to enhance the synergistic anticancer efficiency under a. The cellular studies revealed that CAI@TD could produce oxygen and H 2 O 2 to heighten the efficacy of PDT and NO and induce necrotic-apoptosis of MDA-MB-231 cells by mitochondria damage, lipid peroxidation, and DNA fragments. Moreover, CAI@TD with 808 nm laser irradiation achieved a significant inhibition on the xenograft tumor growth. This work provides an efficient strategy to produce a high amount of ROS for synergistic anticancer therapy, offering a ray of hope in the fight against cancer.
研究领域:
肿瘤学
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纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
·
2025
·
IF 4.1
Hao Wu,Huangshui Ma,Xinghan Wu,Qiang Sun,Lin Feng,Ruifang Jiang,Yanhong Li,Quan Shi
Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. Methods In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). Results Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. Conclusion This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Qiaomei Ke,Ke Jiang,Hong Li,Ling Zhang,Banglin Chen
Mass transfer of bulky molecules, e.g., bioenzymes, particularly for cross-scale multibiomolecules, imposes serious challenges for microporous metal–organic frameworks (MOFs). Here, we create a hierarchically porous MOF heterostructure featuring highly region-ordered micro-, meso-, and macro-pores by growing a microporous ZIF-8 shell onto a hollow Prussian blue core through an epitaxial growth strategy. This allows for localized loading of large bioenzyme glucose oxidase (GOx) and small drug 5-fluorouracil (5-FU) within specific pores simultaneously and triggers unique guest-carrier cooperative anticancer capabilities. The stable ZIF-8 outer layer effectively blocks the core pores, preventing the undesired leakage of GOx into normal tissues. The acidity-induced ZIF-8 degradation gradually releases Zn2+ and loaded 5-FU for chemotherapy under acidic tumor microenvironments. With the loss of the shielding effect of the ZIF-8 coating, the released GOx depletes intratumoral glucose (Glu) for starvation therapy. Notably, an accelerated cascade reaction occurs between ZIF-8 decomposition and GOx release, facilitated by the modulator factor of Glu. This culminates in the realization of synergistic cancer therapy, as comprehensively demonstrated by in vitro and in vivo experiments, as well as transcriptome sequencing analyses. Our work not only introduces a hierarchically porous MOF heterostructure with highly region-ordered pores but also provides a perspective for guest-carrier cooperative anticancer therapy.
研究领域:
材料科学
·
纳米技术
·
癌症研究
·
生物医学工程
✓ 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）