AAPS PHARMSCITECH
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2021
·Vol. 22
·期 4
·1-13
·
IF 3.246
Xu Ying,Tang Lei,Chen Peng,Chen Mei,Zheng Miaomiao,Shi Feng,Wang Yanchun
A novel albumin polymer hybrid with a core–shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n -butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein–PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.
研究领域:
药学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2020
·Vol. 46
·期 6
·2137-2149
·
IF 3.098
Lijia Pan,Litong Nie,Sheng Yao,Aiwei Bi,Yang Ye,Yeming Wu,Zhen Tan,Zhixiang Wu
The prognosis of high‑risk neuroblastoma remains poor. Clinical first‑line drugs for treating neuroblastoma have been developed over the previous half‑century; however, progress in the identification of new drugs with high efficiency is required. Bufalin, one of the major components of extracts obtained from the venom of the Chinese toad Bufo gargarizans, which is used to treat heart failure in Asian Pacific countries, has been reported to be a potential drug against multiple types of tumor; however, the detailed mechanisms underlying its antitumor activities remain unclear, largely due to lack of knowledge regarding its targets. In the present study, bufalin was revealed to exhibit potent antitumor effects against neuroblastoma, both in vitro and in vivo, using cell proliferation, colony formation, Transwell migration and flow cytometry assays, as well as a nude mouse subcutaneous xenograft model. Moreover, a chemically modified bufalin probe was designed to identify the potential targets of bufalin in neuroblastoma via chemical proteomics. With this strategy, it was revealed that the electron transport chain (ETC) on the inner membrane of mitochondria may contain potential targets for bufalin, and that bufalin‑induced mitochondrial‑dependent apoptosis may be caused by disruption of the ETC. Collectively, the present study suggests that bufalin may a promising drug for chemotherapy against neuroblastoma, and provides a foundation for further studies into the antitumor mechanisms of bufalin.
研究领域:
肿瘤学
·
药理学
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细胞生物学
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化学蛋白质组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Guochun Yang,Kun Yu,Lin Peng,Peng Li,Jianan Chen,Meiyu Yang,Jiachao Feng,Zhanpan Wu,Wancun Wang,Anguo Hou,Wenbin Jin
Glycyrrhizic acid (GL) entirely substitutes cholesterol as a bioactive liposomal membrane stabilizer, embodying a “drug-in-as-excipient” design. • A Quality-by-Design (QbD) approach with Box-Behnken optimization ensures formulation robustness and high bufalin entrapment efficiency (88.83%). • Dual targeting via GL-receptor and galactose-ASGPR interactions quantitatively verified by tumor targeting index (TTI) and AUTC metrics. • Gal-BF-GL-Lps achieves a 1.8-fold reduction in IC 50 , potent ROS induction, and mitochondrial apoptosis in H22 hepatoma cells. • Gal-BF-GL-Lps yields a 72.76% tumor volume inhibition rate and favorable biocompatibility in an orthotopic hepatocellular carcinoma model. HCC remains a major therapeutic challenge, and the clinical application of BF is severely limited by its poor solubility, narrow therapeutic window, and systemic toxicity. To address these obstacles, we designed a galactose-modified (Gal), glycyrrhizic acid (GL)-based liposomal system (Gal-BF-GL-Lps) that embodies a “drug-in-as-excipient” philosophy. In this design, the amphiphilic GL was introduced to replace cholesterol entirely, simultaneously functioning as a membrane stabilizer, a therapeutic synergist, and an active ligand for the glycyrrhetinic acid receptor overexpressed on hepatoma cells. The formulation was systematically optimized using a Box-Behnken design within a Quality-by-Design framework, yielding a robust preparation with an entrapment efficiency of 88.83% and a mean particle size of 131.67 nm. The surface decoration with a galactose modified ligand (Gal) further established a dual-targeting mechanism by engaging the asialoglycoprotein receptor. In vitro , Gal-BF-GL-Lps dramatically enhanced cellular uptake by H22 hepatoma cells, potentiating intracellular reactive oxygen species generation and mitochondrial membrane depolarization, which culminated in a superior apoptotic rate and a 1.8-fold lower IC 50 compared to free BF. In vivo real-time fluorescence imaging and the quantitative analysis of the tumor targeting index (TTI) and the area under the TTI-time curve (AUTC) verified the exceptional tumor-homing capacity and prolonged retention of Gal-BF-GL-Lps. This precise targeting translated into powerful antitumor efficacy in an orthotopic HCC mouse model, achieving a tumor volume inhibition rate of 72.76% and significantly downregulating key serum biomarkers (AFP, GPC-3, DCP) and inflammatory cytokines, while concurrently alleviating tumor-induced immunosuppression. Crucially, systematic biocompatibility assessments confirmed the excellent safety profile of Gal-BF-GL-Lps. This integrated, QbD-driven nanoplatform leverages the bioactive carrier material itself to achieve dual-targeted delivery and synergistic therapy, offering a highly translatable strategy for HCC treatment. Download: Download high-res image (333KB) Download: Download full-size image
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DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Tao Liu,Tingting Jia,Xia Yuan,Cheng Liu,Jian Sun,Zhenhua Ni,Jian Xu,Xuhui Wang,Yi Yuan
Background Development of polymeric prodrugs of small molecular anticancer drugs has become one of the most promising strategies to overcome the intrinsic shortcomings of small molecular anticancer drugs and improve their anticancer performance.Materials and methods In the current work, we fabricated a novel octreotide (Oct)-modified esterase-sensitive tumor-targeting polymeric prodrug of bufalin (BUF) and explored its anticancer performance against somatostatin receptor 2 overexpressing breast cancer.Results The obtained tumor-targeting polymeric prodrug of BUF, P(oligo[ethylene glycol] monomethyl ether methacrylate [OEGMA]-co-BUF-co-Oct), showed a nanosize dimension and controlled drug release features in the presence of esterase. It was demonstrated by in vitro experiment that P(OEGMA-co-BUF-co-Oct) showed enhanced cytotoxicity, cellular uptake, and apoptosis in comparison with those of free BUF. In vivo experiment further revealed the improved accumulation of drugs in tumor tissues and enhanced anticancer performance of P(OEGMA-co-BUF-co-Oct).Conclusion Taken together, this study indicated that polymeric prodrug of BUF holds promising potential toward the treatment of somatostatin receptor 2 overexpressing breast cancer.
研究领域:
药学
·
肿瘤学
·
药物递送系统
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Xiao-jing Shi,Yan-yan Qiu,Hui Yu,Cheng Liu,Yu-xia Yuan,Pei-hao Yin,Tao Liu
A well-defined multifunctional brush-type polymeric prodrug covalently linked with an anticancer drug (bufalin, BUF), a tumor-targeting peptide (RGD), and an endosome-escaping polymer, poly( N,N -diethylaminoethyl methacrylate- co -butyl methacrylate (P(DEA- co -BMA)), was developed. Its anticancer performance against colon cancer was investigated in vitro and in vivo. Reversible addition-fragmentation transfer (RAFT) polymerization of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), 2-((3-( tert -butoxy)-3-oxopropyl)thio)ethyl methacrylate (BSTMA), and 2-(2-bromoisobutyryloxy)ethylmethacrylate (BIEM) afforded the multifunctional random copolymer, P(OEGMA- co -BSTMA- co -BIEM), in which hydrophilic POEGMA can stabilize nanoparticles in water, PBSTMA can be converted into carboxyl groups, and PBIEM can be employed as a macromolecular atom radical transfer polymerization (ATRP) initiator. The ATRP of DEA and BMA using P(OEGMA- co -BSTMA- co -BIEM) as a macromolecular ATRP initiator led to the formation of the pH-responsive brush-type copolymer, P(OEGMA- co -BSTMA)- g -P(DEA- co - BMA). After hydrolysis by trifluoroacetic acid and post-functionalization the final polymeric prodrug, P(OEGMA- co -BUF- co -RGD)- g -P(DEA- co -BMA), was obtained with a drug content of ∼7.8 wt%. P(OEGMA- co -BUF- co -RGD)- g -P(DEA- co -BMA) can be assembled into nanoparticles (BUF- NP-RGD) in aqueous solution with a diameter of 148.4 ± 0.7 nm and a zeta potential of −7.6 ± 0.4 mV. BUF-NP-RGD exhibited controlled drug release in the presence of esterase. Additionally, P(OEGMA- co - BSMA)- g -P(DEA- co -BMA) showed a significant hemolysis effect at a pH comparable to that of endosomes/lysosomes. Cell viability and a tumor-bearing nude mouse model were employed to evaluate the anticancer efficacy of BUF-NP-RGD. It was revealed that BUF-NP-RGD showed improved anticancer performance compared with that of free BUF both in vitro and in vivo. Histological and immunochemical analysis further demonstrated that BUF-NP-RGD exhibited improved cell apoptosis, angiogenesis inhibition, and an anti-proliferation effect.
研究领域:
药学
·
聚合物化学
·
癌症研究
·
药物递送系统
✓ 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）