Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Abstract

Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.

In Vitro Targeted Delivery of Simvastatin and Niacin to Macrophages Using Mannan-Grafted Magnetite Nanoparticles

“…There are limited reports on the enzyme-sensitive drug delivery systems, and most importantly, pH-sensitive release is between 30 and 90% . The doxorubicin releasing profile from β-cyclodextrin NPs, simvastatin release from Ca-Gly-Maltose-D16F7, and methotrexate from pectin NPs at pH = 5 was reported to be 37, 54, and 90%, respectively which are comparable with our system. ,, …”

“…The unwanted leakage of niacin and simvastatin in N@MN-MNPs and S@MN-MNPs is calculated to be 19.22 and 14.38, which is much lower than previously reported scaffolds such as magnetic chitosan micelles with 65% release and pectin magnetic NPs with 60 and 34% release, respectively. The reported leakage in other nanocarriers like Chitosan@β-cyclodextrin (30%) and Ca-Gly-Maltose-D16F7 (25%) was also higher than our delivery system. ,− The enzyme-mediated release of niacin and simvastatin was estimated to be 67.23 and 79.51%, respectively. In our delivery system, active lysosomal enzymes, α- d -mannosidase, are predicted to act as a polymer degrading agent.…”

“…71 The doxorubicin releasing profile from β-cyclodextrin NPs, simvastatin release from Ca-Gly-Maltose-D16F7, and methotrexate from pectin NPs at pH = 5 was reported to be 37, 54, and 90%, respectively which are comparable with our system. 68,72,73 The use of biocompatible NPs is favorable with the aim of increasing drug uptake efficiency, reducing unwanted side effects, and preventing premature drug release. We used macrophages, HUVECs, and hepatocytes for biocompatibility experiments.…”

Preparation of an amphiphilic peptide (P13) with proton sponge effect and analysis of its antitumor activity

“…However, for multifunctional drug delivery systems that need to overcome multiple physiological barriers, lysosome escape is a step that cannot be ignored. That is, after drug-loaded carriers enter cells, they can reach the targeted position and produce effective drug response only when they are not captured by organelles with acidic environments, such as lysosomes and phagocytic vesicles [2]. Therefore, it is very important to design a drug carrier with the ability to escape lysosomes to improve drug delivery efficacy and achieve organelle targeting.…”