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AS101-Loaded PLGA-PEG Nanoparticles for Autoimmune Regulation and Chemosensitization
Rahul Kumar Mishra1, Vijay Bhooshan Kumar1, Lea Monteran2
1Bar-Ilan Institute for Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Abstract:
The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for antitumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated a significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at a conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bell-shaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving an optimal antimetastatic effect.
Insights
Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) encapsulated in nanoparticles (AS101-NPs) enhances anti-tumor effects. AS101-NPs increased macrophage counts and inhibited melanoma lung metastasis in mice.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Therapeutic nanoparticles (NPs) can modify drug efficacy.
- Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) is an immunomodulator with anti-tumor potential.
- Controlling pharmacokinetics of AS101 is crucial for minimizing side effects.
Purpose of the Study:
- To develop and characterize AS101-loaded nanoparticles (AS101-NPs) using poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG).
- To evaluate the in vivo efficacy of AS101-NPs in sensitizing tumors to chemotherapy and inhibiting metastasis.
Main Methods:
- AS101-NPs were synthesized via nanoprecipitation.
- Physical characteristics of AS101-NPs were evaluated.
- In vivo studies in mouse models assessed peritoneal macrophage counts and B16 melanoma lung metastasis inhibition.
Main Results:
- AS101-NPs significantly increased peritoneal macrophage counts compared to conventional AS101 administration.
- AS101-NPs demonstrated significant inhibition of B16 melanoma lung metastasis.
- A bell-shaped dose-response curve was observed, indicating optimal dosage is critical.
Conclusions:
- AS101-NPs represent a promising drug delivery system for enhancing AS101's immunomodulatory and anti-metastatic effects.
- Nanoparticle encapsulation improves AS101's biological activity and therapeutic potential.
- Optimizing administration frequency is key for maximizing AS101's anti-metastatic efficacy.
