JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Guiping Yuan,Yifan Zhang,Shiqun Shao,Zhuxian Zhou,Jianbin Tang,Jiajia Xiang,Youqing Shen
Drug self-delivery systems (DSDSs) have been extensively exploited to enhance drug loading capacity and avoid excipient-related toxicity issues. However, deficient tumor targeting, inferior tumor permeability, prominent burst release, and nonspecific subcellular distribution remain major obstacles. Herein, we reported a ROS-responsive amphiphilic prodrug (CPT-S-NO) synthesized by the conjugation of zwitterionic tertiary amine-oxide (TAO) moiety and hydrophobic camptothecin (CPT) through a thioether linkage, which formed a nanoparticulate DSDS in an aqueous solution. CPT-S-NO, compared with CPT-11 and the water-soluble TAO-modified CPT prodrug (CPT-NO), exhibited prolonged blood circulation, enhanced tumor accumulation, deep tumor penetration, efficient mitochondrial targeting, and ROS-activated drug release to induce mitochondrial dysfunction, corporately conducing to the superior antitumor efficacy in vivo. This TAO decoration strategy promises potential applications in designing multipotent DSDSs for various drugs.
研究领域:
药理学
·
肿瘤学
·
纳米医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2017
·
IF 6.402
Shenwu Zhang,Jibin Guan,Mengchi Sun,Dong Zhang,Haotian Zhang,Bingjun Sun,Weiling Guo,Bin Lin,Yongjun Wang,Zhonggui He,Cong Luo,Jin Sun
Breast cancer leads to high mortality of women in the world. Docetaxel (DTX) has been widely applied as one of the first-line chemotherapeutic drugs for breast cancer therapy. However, the clinical outcome of DTX is far from satisfaction due to its poor drug delivery efficiency. Herein, a novel disulfide bond bridged oleate prodrug of DTX was designed and synthesized to construct self-delivering prodrug-based nanosystem for improved anticancer efficacy of DTX. The uniquely engineered prodrug-nanoassemblies showed redox-responsive drug release, increased cellular uptake and comparable cytotoxicity against 4T1 breast cancer cells when compared with free DTX. In vivo, oleate prodrug-based nanoparticles (NPs) demonstrated significantly prolonged systemic circulation and increased accumulation in tumor site. As a result, prodrug NPs produced a notable antitumor activity in 4T1 breast cancer xenograft in BALB/c mice. This prodrug-based self-assembly and self-delivery strategy could be utilized to improve the delivery efficiency of DTX for breast cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 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
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2015
·Vol. 25
·期 20
·2961-2971
·
IF 11.805
Kai Han,Qi Lei,Shi-Bo Wang,Jing-Jing Hu,Wen-Xiu Qiu,Jing-Yi Zhu,Wei-Na Yin,Xu Luo,Xian-Zheng Zhang
In this paper, a self-delivery system PpIX-PEG-(KLAKLAK) 2 (designated as PPK) is fabricated to realize mitochondria-targeted photodynamic tumor therapy. It is found that the PPK self-delivery system exhibited high drug loading efficacy as well as novel capacity in generation of intracellular reactive oxygen species (ROS). This study also indicated that the photochemical internalization effect of the photosensitizer protoporphyrin IX (PpIX) under a short time light irradiation improved the cellular internalization of PPK. On the contrary, PPK could target to the subcellular organelle mitochondria due to the presence of proapoptosis (KLAKLAK) 2 peptide. Importantly, the in situ generation of ROS in mitochondria enhanced the photodynamic therapy efficacy under another long time irradiation, leading to significant cell death with decreased mitochondrial membrane potential. Besides, relative high tumor accumulation, minimal systemic cytotoxicity and efficacious long-term tumor inhibition in vivo are also confirmed by using a murine model. All these results demonstrated the self-delivery system PPK with a dual-stage light irradiation strategy is a promising nanoplatform for tumor treatment.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
DOI
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 9
·期 1
·1901100
·
IF 6.27
Wen Ma,Sui-Nan Sha,Pei-Ling Chen,Meng Yu,Jian-Jun Chen,Chao-Bo Huang,Bin Yu,Yun Liu,Li-Han Liu,Zhi-Qiang Yu
Nowadays, cell membrane-targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane-targeted self-delivery theranostic chimeric peptide CMP-PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real-time therapeutic feedback. Self-assembled CMP-PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP-PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)-carboxyfluorescein (FAM) and 4-(dimethylaminoazo)-benzene-4-carboxylic acid (Dabcyl). More importantly, CMP-PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP-PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp-Glu-Val-Asp (DEVD) is subsequently cleaved by activated caspase-3 and activated caspase-7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase-3 in vitro and in vivo to feedback real-time PDT therapeutic efficacy. In general, a novel cell membrane-targeted self-delivery theranostic chimeric peptide offers new promise for effective imaging-guided PDT.
研究领域:
肿瘤学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Xin Wan,Wensong Wang,Yutian Zhou,Xiaoyu Ma,Meng Guan,Fan Liu,Si Chen,Jin-Xuan Fan,Guo-Ping Yan
Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Yibin Liu,Fuan Deng,Rongrong Zheng,Xiayun Chen,Linping Zhao,Baixue Yu,Ali Chen,Xueyan Jiang,Hong Cheng,Shiying Li
Tumor vascular blockade is a promising strategy for adjuvant cancer treatment. In this work, a self-delivery nanomedicine is developed based on a vascular disruptor and photosensitizer for tumor synergistic therapy. Specifically, this nanomedicine (designated as CeCA) is comprised of combretastatin A4 (CA4) and chlorine e6 (Ce6) by self-assembly technique. Among which, CA4 could not only induce tubulin inhibition for chemotherapy but also disrupt the vasculature to cause tumor hemorrhage. Moreover, Ce6 is able to generate lots of singlet oxygen ( 1 O 2 ) for synergistic photodynamic therapy (PDT) under light irradiation . It is interesting that the carrier-free CeCA possessed a favorable stability and an improved cellular uptake behavior. After intravenous administration, CeCA prefers to accumulate at tumor site for vascular disruption-supplemented chemo-photodynamic therapy. Notably, CeCA is prepared without additional carriers, which avoids the system toxicity raised by excipients . Consequently, CeCA greatly inhibits the tumor growth and leads to a low side effect in vivo . It might open a window in the development of self-supplementary nanomedicine for synergistic tumor treatment.
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
ACS Nano
·
2023
·
IF 17.1
Wenzhe Xu,Yang Chen,Ruixu Yang,Yiying Fu,Wanxin Zhuang,Yonggang Wang,Yi Liu,Hao Zhang
Nanoprecipitation, which is achieved through the diffusion and precipitation of drug molecules in blended solvent and antisolvent phases, is a classic route for constructing nanodrugs (NDs) and previously directed by diffusion-controlled theory. However, the diffusion-controlled mechanism is out of date in the recent preparation of self-delivery supramolecular NDs (SDSNDs), characterized by the construction of drug nanoparticles through supramolecular interactions in the absence of carriers and surfactants. Herein, a “reaction”-like complement, contributed from supramolecular interactions, is proposed for the preparation of naphthoquinone SDSNDs. Different from the diffusion-controlled process, the formation rate of SDSNDs via the “reaction”-like process is almost constant and highly dependent on the supramolecular interaction-determined Gibbs free energy of molecular binding. Thus, the formation rate and drug availability of SDSNDs are greatly improved by engineering the supramolecular interactions, which facilitates the preparation of SDSNDs with expected sizes, components, and therapeutic functions. As a deep understanding of supramolecular-interaction-involved nanoprecipitation, the current “reaction”-like protocol not only provides a theoretical supplement for classic nanoprecipitation but also highlights the potential of nanoprecipitation in shaping self-assembled, coassembled, and metal-ion-associated SDSNDs.
研究领域:
药剂学
·
纳米医学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yun Deng,Wangxiang Yan,Dalong Shu,Li Zhu,Songling Chen,Yu Chen
Oral squamous cell carcinoma (OSCC) is a common oral malignancy. However, conventional chemotherapeutic strategies present many limitations. To overcome these challenges, a cell membrane-camouflaged amphiphilic self-delivery nano-prodrug was developed for the targeted treatment of OSCC. In this system, the hydrophobic anticancer drug methotrexate (MTX) and the hydrophilic drug gemcitabine (GEM) were conjugated via amide bonds to form an amphiphilic drug-drug conjugate (ADDC), which self-assembled into nanoparticles (MG NPs). Phospholipids were modified with T7 peptide, capable of targeting the highly expressed transferrin receptor (TFR) on tumor cell surfaces, and subsequently loaded onto red blood cell membranes (RBCM) to prepare T7 peptide-modified RBCM (T7-RBCM). The MG NPs were then encapsulated with T7-RBCM by co-extrusion to form T7-RBCM@MG NPs. In vitro studies demonstrated that T7-RBCM@MG NPs were more efficiently internalized by tumor cells due to specific recognition between the T7 peptide and TFR, exhibited stronger inhibitory activity against SCC-7 cells, and significantly induced apoptosis. In vivo experiments confirmed that T7-RBCM@MG NPs exhibited favourable biosafety, prolonged circulation, and enhanced tumor-targeting delivery, resulting in significant tumor growth inhibition without notable toxicity to major organs.
研究领域:
肿瘤学
·
纳米医学
·
药剂学
·
分子靶向治疗
·
转化医学
·
生物材料
·
头颈肿瘤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Shenzhen Ren,Mingzhe Zhang,Chunxiu Cai,Ning Zhang,Zijia Wang,Gen Li,Quan Liu,Hailiang Zhu,Hailong An,Yafei Chen
Sonodynamic therapy (SDT) is an efficient non-invasive strategy for treating breast cancer. However, the therapeutic efficacy of SDT is greatly limited by various defense mechanisms in the tumor microenvironment, particularly the overexpression of B-cell lymphoma-2 (Bcl-2). In this study, based on drug self-delivery systems, a carrier-free ultrasound-responsive polyphenol nanonetwork (GTC) was developed to enhance SDT by inhibiting Bcl-2. A one-pot method, involving the interaction of the polyphenolic Bcl-2 inhibitor gossypol (GOS), transferrin, and the sonosensitizer chlorin e6 (Ce6), was used to synthesize the GTC. The GTC was efficiently internalized by MDA-MB-231 and 4T1 cells through specific binding to transferrin receptors, and no external carriers were needed. After cellular internalization, GOS increased the lethality of Ce6-mediated SDT by reducing the expression of the Bcl-2 protein, which caused multiple toxic effects. RNA-seq analysis confirmed the transcriptomic alterations in oxidative stress and apoptotic pathways induced by the GTC nanosystem. In vivo studies revealed that GOS-assisted SDT not only eliminated tumors through sonodynamic effects and triggered immunogenic cell death but also enhanced sono-immunotherapy, thus effectively suppressing distant tumors and metastasis. This study might provide insights into carrier-free nanomedicines for SDT-based synergistic tumor therapy.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Shao-Yi Chen,Lin-Ping Zhao,Zu-Xiao Chen,Chu-Yu Huang,Ren-Jiang Kong,Yu-Qing Wang,Da-Wei Zhang,Shi-Ying Li,Hui-Hui Ti,Hong Cheng
ABSTRACT Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. Statement of Significance Autophagy is a “double-edged sword” in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.
研究领域:
生物医学工程
·
癌症研究
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2017
·Vol. 27
·期 25
·1700220
·
IF 12.124
Li-Han Liu,Wen-Xiu Qiu,Yao-Hui Zhang,Bin Li,Chi Zhang,Fan Gao,Lu Zhang,Xian-Zheng Zhang
The cell membrane is the most important protective barrier in living cells and cell membrane targeted therapy may be a high-performance therapeutic modality for tumor treatment. Here, a novel charge reversible self-delivery chimeric peptide C 16 –PRP–DMA is developed for long-term cell membrane targeted photodynamic therapy (PDT). The self-assembled C 16 –PRP–DMA nanoparticles can effectively target to tumor by enhanced permeability and retention effect without additional carriers. After undergoing charge reverse in acidic tumor microenvironment, C 16 –PRP–DMA inserts into the tumor cell membrane with a long retention time of more than 14 h, which is very helpful for in vivo applications. It is found that under light irradiation, the reactive oxygen species generated by the inserted C 16 –PRP–DMA would directly disrupt cell membrane and rapidly induce cell necrosis, which remarkably increases the PDT effect in vitro and in vivo. This novel self-delivery chimeric peptide with a long-term cell membrane targeting property provides a new prospect for effective PDT of cancer.
研究领域:
癌症研究
·
药学
·
生物技术
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）