Jinyao Li

ROS-responsive supramolecular antimicrobial peptides-based nanoprodrugs for cervical cancer therapy

Although antimicrobial peptides (AMPs) as a promising natural drugs can efficiently inhibit cervical cancer, poor bioavailability, low tumor selectivity, and non-selective toxicity still hinder its further application in vivo. In order to effectively address these challenges, we have developed a reactive oxygen species (ROS)-responsive targeting nanoprodrug designed for selective therapy of cervical cancer. Such nanoprodrugs (CEC-OxbCD) are fabricated by the supramolecular self-assembly of the modified β-cyclodextrin (β-CD) and AMPs. Antimicrobial peptide, CecropinXJ (CEC), is a cationic antibacterial peptide isolated from 3rd instar larvae of Bombyx mori from Xinjiang, China. OxbCD is an oxidation-responsive β-cyclodextrin material. CEC-OxbCD were synthesized using the nanoprecipitation/self-assembly method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behaviour of CEC-OxbCD were characterised. In vitro and in vivo anti-cancer activities were also evaluated. Nanoprodrugs can be effectively disassembled under stimuli of the tumor- endogenous ROS, resulting in a rapid and on-demand release of antimicrobial peptides (AMPs) with a release rate of 90 %. Furthermore, both in vitro and in vivo experimental results demonstrate that our nanoprodrugs exhibit remarkable therapeutic efficacy against cervical cancer. This work not only provides an effective and promising therapeutic strategy for cervical cancer, but also explores a novel application for AMPs.

Potential Mechanisms of Plant-Derived Natural Products in the Treatment of Cervical Cancer

Cervical cancer is the second most common gynecological malignancy globally; it seriously endangers women’s health because of its high morbidity and mortality. Conventional treatments are prone to drug resistance, recurrence and metastasis. Therefore, there is an urgent need to develop new drugs with high efficacy and low side effects to prevent and treat cervical cancer. In recent years, plant-derived natural products have been evaluated as potential anticancer drugs that preferentially kill tumor cells without severe adverse effects. A growing number of studies have shown that natural products can achieve practical anti-cervical-cancer effects through multiple mechanisms, including inhibition of tumor-cell proliferation, induction of apoptosis, suppression of angiogenesis and telomerase activity, enhancement of immunity and reversal of multidrug resistance. This paper reviews the therapeutic effects and mechanisms of plant-derived natural products on cervical cancer and provides references for developing anti-cervical-cancer drugs with high efficacy and low side effects.

Cecropin-Loaded Zeolitic Imidazolate Framework Nanoparticles with High Biocompatibility and Cervical Cancer Cell Toxicity

Cecropins (CECs) are insect venom-derived amphiphilic peptides with numerous pharmacological effects, including anti-inflammatory, antibacterial, antiviral, and anti-tumor activities. Cecropins induce tumor cell death by disrupting phospholipid membrane integrity. However, non-specific cytotoxicity and in vivo rapid degradation limit clinical application. Nanotechnologies provide novel strategies for tumor eradication, including nanocarriers that can precisely target drugs to tumor tissue. We report the fabrication of CEC-encapsulated zeolitic imidazolate framework 8 (ZIF-8) nanoparticles (CEC@ZIF-8 NPs) via the preparation of CEC@ZIF-8 NPs in pure water by one-pot stirring. This method yielded morphologically uniform NPs with 20 wt% drug loading capacity and 9% loading efficiency. The NP formulation protected CECs from proteasome degradation, enhanced peptide bioavailability, promoted HeLa tumor cell uptake, and increased antitumor efficacy compared to free CECs. In conclusion, this ZIF-8 encapsulation strategy may enhance the clinical applicability of CECs and other antitumor peptides.