ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yongju He,Xiangjie Tian,Xingyu Fan,Xiyu Gong,Songwen Tan,Anqiang Pan,Shuquan Liang,Hui Xu,Fangfang Zhou
The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H2 and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H2 to the deep part of tumors for effective gas therapy. Ammonia borane (AB) is chosen as the H2 prodrug that can be effectively loaded into UAMSN by hydrogen-bonding adsorption. Gelatin is used as the substrate of MMP-2 to trigger size change and block AB inside UAMSN during blood circulation. PEG is introduced to further increase the particle size and endow the nanoparticle with long blood circulation to achieve effective tumor accumulation via the EPR effect. After accumulation into the tumor site, MMP-2 promptly digests gelatin to expose UAMSN loading AB for deep tumor penetration. Upon stimulation by the acidic tumor microenvironment, AB decomposes into H2 for further intratumor diffusion to achieve effective hydrogen therapy. Consequently, such a simultaneous deep tumor penetration of nanocarriers and H2 results in an evident suppression on tumor growth in a 4T1 tumor-bearing model without any obvious toxicity on normal tissues. Our synthetic nanosystem provides a promising strategy for the development of nanomedicines with enhanced tumor permeability and good biosafety for efficient tumor treatment.
研究领域:
肿瘤学
·
纳米医学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2024
·
IF 6.1
Jihong Ma,Haiyan Yang,Xue Tian,Fanhu Meng,Xiaoqing Zhai,Aimei Li,Chuntao Li,Min Wang,Guohui Wang,Chunbo Lu,Jingkun Bai
Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self-assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP-2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP-2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4 + T cells. Ultimately, DI/Pep1 attenuated tumor-associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 54
·31264-31273
·
IF 3.049
Wei Li,Cheng Tao,Jiexin Wang,Yuan Le,Jianjun Zhang
The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Xiuting He,Zhongcheng Cao,Nuannuan Li,Liuxiang Chu,Jiazhen Wang,Chunyan Zhang,Xiaoyan He,Xiaoyan Lu,Kaoxiang Sun,Qingguo Meng
7-Ethyl-10-hydroxycamptothecin (SN-38)-loaded polyethylene glycol-GPLGVRG-poly β-benzyl- l -aspartic acid (PEG-GPLGVRG-PBLA) self-assemblies were successfully prepared using a classical nanoprecipitation method to give an enzyme-responsive nano-drug delivery system. The PEG-GPLGVRG-PBLA/SN-38 self-assemblies were characterized by transmission electron microscopy , dynamic light scattering , and high-performance liquid chromatography. The encapsulation efficiency was 91.7 ± 1.21% and the drug loading was 16.6 ± 0.93%. The 12 h in vitro release of SN-38 from PEG-GPLGVRG-PBLA/SN-38 treated with MMP-2 was 73.2 ± 2.05%, which was significantly higher than that for the group without MMP-2, demonstrating the enzyme-responsiveness of the nano-drug delivery system. In addition, the cellular uptake and tumor accumulation of PEG-GPLGVRG-PBLA were better than those of PEG-PBLA, and the blank PEG-GPLGVRG-PBLA showed high biocompatibility . These findings indicate that the enzyme-responsive nano SN-38 delivery system could provide new opportunities in tumor therapy.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 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）