Abstract
We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in cellular responses in vitro. The PEBCA NPs had the highest uptake both in the patient-derived breast cancer xenograft MAS98.12 and in lymph nodes, and therefore, they are the most promising of these NPs for delivery of cancer drugs. High-resolution magic angle spinning magnetic resonance (HR MAS MR) spectroscopy did not reveal any differences in the metabolic profiles of tumors following injection of the NPs, but the PEBCA NPs resulted in higher tumor infiltration of the anti-tumorigenic M1 macrophages than obtained with the two other NPs. The PEBCA NPs also increased the ratio of M1/M2 (anti-tumorigenic/pro-tumorigenic) macrophages in the tumors, suggesting that these NPs might be used both as a vehicle for drug delivery and to modulate the immune response in favor of enhanced therapeutic effects.
Highlights
nuclear magnetic resonance (NMR) showed that the number of ethylene units per nm2 on the particles was similar for fluorescently labeled poly(n-butyl cyanoacrylate) (PBCA) and poly(octyl cyanoacrylate) (POCA), whereas poly(2-ethyl-butyl cyanoacrylate) (PEBCA) particles had approximately 40% more ethylene units
Bution, in addition accumulation in lymph of the NPs compared to the two other poly(alkyl cyanoacrylate) (PACA) NPs
Injection of the PEBCA NPs led to an increased compared to the two other PACA NPs
Summary
Chemotherapy during recent years has improved the treatment and prognosis of different cancers, there are still challenges with severe adverse effects, drug resistance, Nanomaterials 2021, 11, 1140. The use of drug-loaded nanoparticles (NPs) could improve cancer therapy. Several such products have reached the market, and many new product candidates are presently in clinical trials [1]. The challenges and opportunities of using NPs for cancer drug delivery have been discussed in several reviews [2,3]. One advantage of using NPs for drug delivery is linked to the trapping in tumors due to the enhanced permeability and retention (EPR) effect [4], the importance of this effect is being discussed [5,6]. Drug encapsulation allows for the enhanced solubility of poorly soluble drugs, protection of the drug, prolonged and controlled release, and altered biodistribution
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