Advanced Healthcare Materials
·
2025
·
IF 9.6
Runzhi Xia,Wei Sun,Jiaming Liang,Shidong Wang,Fuqiang Gao,Yawei Liu,Liu Wang,Hongjie Zhang,Chao Ma,Kai Liu
The treatment of osteosarcoma remains challenging due to limitations of chemotherapy. Anticancer peptides present a promising avenue as alternative therapeutic agents; however, they encounter significant drawbacks, including susceptibility to proteolytic degradation and constrained selectivity toward tumor. Herein, a few-shot peptide screening strategy is developed, yielding identification of RT2 (tumor-lytic peptide) and E16 (ionic-responsive self-assembling peptide). Their fusion E16-RT2 (ER) is engineered, exhibiting 175% enhanced tumor-selective cytotoxicity and cancer membrane targeting. By leveraging the dual functionality of ER, an injectable hydrogel encapsulating doxorubicin is developed, enabling gradient dynamics for tumor-specific drug release and sustained therapeutic efficacy (>9 d). Moreover, there is no systemic/organ toxicity in murine models dosed with the therapeutic network. The potential mechanism is proposed: charge-guided ER localization disrupts cancer membrane integrity, enabling therapeutics influx while sparing healthy cells, coupled with network degradation kinetics ensuring prolonged drug retention. This rational design paradigm establishes a clinically translatable platform combining tumor-perturbing peptides with smart biomaterials, effectively overcoming limitations of conventional agents. The demonstrated “safety-efficacy” profile positions this approach as a viable strategy for cancer treatment.
研究领域:
肿瘤学
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药理学
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生物材料科学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Fang Pan,Yueping Li,Yujie Ding,Songwei Lv,Rongrong You,Roja Hadianamrei,Mhd Anas Tomeh,Xiubo Zhao
Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells . In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
研究领域:
肿瘤学
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药学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
APOPTOSIS
·
2018
·Vol. 23
·期 2
·132-142
·
IF 3.967
Hu Cuihua,Chen Xiaolong,Huang Yibing,Chen Yuxin
In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.
研究领域:
肿瘤学
·
药学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2024
·
IF 3.7
Chun-Yi Wang,Dairong Li,Xiufeng Chen,Zhixiong Chen
The low drug resistance, excellent cancer cell targeting, and anticancer benefits of anticancer peptides (ACPs) make them an attractive antitumor drug option. On the other hand, enzymes readily break down in many ACPs after delivery due to their non-specific toxicity. Consequently, drug delivery systems (DDSs) are necessary to avoid the peptides' dissociation and persuade targeted delivery. The cationic amphiphilic anticancer peptide, G(IIKK) 3 I-NH 2 (G3), was developed in this work using a high-performance microfluidic system, which encapsulates the zeolitic imidazolate framework (ZIF-8). The ACPs-loaded nanoparticles (NPs) were efficiently and quickly mixed using the microfluidic system, resulting in NPs with tunable properties. The encapsulation efficacy was high, and the production rate was 120 mL/min. The microfluidic technique-based ZIF-8 fabrication demonstrated better size homogeneity, as evidenced by a decreased polydispersity index (PDI) compared to the conventional technique. The hemolytic effect was much diminished, and a pH-controlled release of the G3 peptides was achieved by encapsulating G(IIKK) 3 I-NH 2 (termed as G3@ZIF-8) into the ZIF-8. Owing to the improved cell absorption by the ZIF-8, G3@ZIF-8 demonstrated a stronger anticancer impact than the free G3 peptide at identical concentrations. In addition to damaging the mitochondrial membrane of HCT 116 colorectal cancer cells, the NPs were able to suppress the proliferation. Consequently, ACP-based cancer therapy can be expanded by developing G3-loaded ZIF-8-NPs, offering an option technique for ACP-based delivery.
研究领域:
癌症研究
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药学科学
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纳米技术
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生物医学工程
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DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Jinguo Qiu,Mhd Anas Tomeh,Yi Jin,Bo Zhang,Xiubo Zhao
Anticancer peptides (ACPs) are promising antitumor drugs owning to their great cancer cell targeting and anticancer effects as well as low drug resistance. However, many of the ACPs have non-specific toxicity and can be easily degraded by the enzymes after administration. Therefore, drug delivery systems (DDSs) are required to shield these peptides from degradation and induce targeted delivery. In this paper, a high performance microfluidic device was used to fabricate the zeolitic imidazolate framework (ZIF-8) encapsulating an ACP (At3) recently developed by our group. The microfluidic device allowed for efficient and rapid mixing to generate ACP loaded nanoparticles (NPs) with controllable properties at high production rate (120 mL/min) and high encapsulation efficiency. The ZIF-8 NPs synthesised by microfluidic processing showed lower polydispersity index (PDI) than the conventional method, demonstrating an improved size uniformity. Encapsulating At3 into the ZIF-8 ( [email protected] ) significantly reduced the hemolytic effect and provided a pH-controlled release of At3 peptide. [email protected] showed higher anticancer effect than the unloaded peptide at the same concentration due to the enhanced cell uptake by the ZIF-8 NPs. The NPs were able to inhibit the growth of the multicellular tumour spheroids (MCTSs) and damage the mitochondrial membrane of the MCF-7 breast cancer cells. In vivo experiments demonstrated that the [email protected] NPs inhibited the growth of MCF-7 tumours in nude mice without changing the biochemical properties of the blood or the histopathological properties of vital organs. Therefore, the development of At3 loaded NPs provides an alternative approach in ACP delivery which can broaden the application of ACP-based cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
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