Ligand-Modified Erythrocyte Membrane-Cloaked Metal–Organic Framework Nanoparticles for Targeted Antitumor Therapy

Abstract

Systemic chemotherapy for treating tumors often leads to serious systemic side effects and affects patient compliance. Although the emerging technology of drug delivery systems (DDSs) can deliver the required cargo to tumor sites, DDSs are limited due to insufficient targeting ability or deficient pharmacokinetics. Herein, we assembled a novel targeting DDS for precision tumor therapy by applying a tumor-targeting polypeptide cyclic RGD (cRGD)modified erythrocyte membrane (eM-cRGD) cloaked on zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) with encapsulated doxorubicin (DOX). For a mass ratio of ZIF-8:DOX = 1:1, the loading capacity was up to 49%. The nanoscale-sized targeting DDS promoted NP accumulation in tumor tissues via enhanced permeability and retention (EPR) effects, and the NPs actively targeted ligands and were then transferred to endosomes. The pH-sensitive carriers released higher DOX levels under the low pH mimicking that of a tumor microenvironment and tumor intracellular organelles, allowing enhanced inhibition of cancer cell growth.

Spray drying-assisted construction of hierarchically porous ZIF-8 for controlled release of doxorubicin

“…DOX enters the cells through endocytosis and move from endosomes to lysosomes. 77,78 Furthermore, compared with free DOX, DOX@HP-ZIF-8 induced more considerable morphological changes in HeLa cells, which is consistent with the viability test results. In summary, it could be concluded that DOX loaded in DOX@HP-ZIF-8 could be released to effectively inhibit the proliferation of tumor cells, thereby achieving good therapeutic efficacy.…”

Nanocarrier-Based Drug Delivery for Melanoma Therapeutics

“…In earlyand late-stage melanoma lung metastasis models, the ELeCt platform can significantly inhibit tumor growth, thereby significantly improving survival [111]. In addition, various commonly used chemotherapeutic agents (e.g., DOX) can be loaded into biodegradable nanoparticles, which can be further manufactured and successfully assembled onto erythrocytes [112,113]. In summary, these studies indicate that the ELeCt platform provides a universal strategy that increases the effectiveness of chemotherapy in treating the lung metastases of melanoma.…”

Biocompatibility and biodegradability of metal organic frameworks for biomedical applications

“…MOFs usually tend to accumulate in liver 94,95 and kidney 96 , as they are the main organs responsible for NPs clearance. Few have reported high accumulations of MOFs in lungs 97 and spleen 98 . Furthermore, in the case of tumor treatment, MOFs tend to accumulate in tumor tissues due to the high permeability of cancer cells 99 .…”