PLGA-Lipid Hybrid Nanoparticles for Overcoming Paclitaxel Tolerance in Anoikis-Resistant Lung Cancer Cells

Abstract

Drug resistance and metastasis are two major obstacles to cancer chemotherapy. During metastasis, cancer cells can survive as floating cells in the blood or lymphatic circulatory system, due to the acquisition of resistance to anoikis—a programmed cell death activated by loss of extracellular matrix attachment. The anoikis-resistant lung cancer cells also develop drug resistance. In this study, paclitaxel-encapsulated PLGA-lipid hybrid nanoparticles (PLHNPs) were formulated by nanoprecipitation combined with self-assembly. The paclitaxel-PLHNPs had an average particle size of 103.0 ± 1.6 nm and a zeta potential value of −52.9 mV with the monodisperse distribution. Cytotoxicity of the nanoparticles was evaluated in A549 human lung cancer cells cultivated as floating cells under non-adherent conditions, compared with A549 attached cells. The floating cells exhibited anoikis resistance as shown by a lack of caspase-3 activation, in contrast to floating normal epithelial cells. Paclitaxel tolerance was evident in floating cells which had an IC50 value of 418.56 nM, compared to an IC50 value of 7.88 nM for attached cells. Paclitaxel-PLHNPs significantly reduced the IC50 values in both attached cells (IC50 value of 0.11 nM, 71.6-fold decrease) and floating cells (IC50 value of 1.13 nM, 370.4-fold decrease). This report demonstrated the potential of PLHNPs to improve the efficacy of the chemotherapeutic drug paclitaxel, for eradicating anoikis-resistant lung cancer cells during metastasis.

Lipid Nanoparticles in Lung Cancer Therapy

“…Building on this, poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles loaded with paclitaxel were studied for their cytotoxic effects on anoikis-resistant lung cancer cells using a method that combined nanoprecipitation and self-assembly. These nanoparticles significantly diminished paclitaxel resistance in both attached and floating cancer cell states, pointing to their potential effectiveness in treating resistant forms of lung cancer, as shown in Figure 2 [16].…”

“…Together, lipid-based nanoparticles, especially the advanced solid lipid-polymer hybrid types, hold significant promise for transforming drug delivery, offering targeted, controlled, and efficient therapeutic molecule transport. The continuous research and Pharmaceutics 2024, 16, 644 3 of 30 development in this area are likely to further refine these systems, overcoming current limitations and paving the way for their widespread application in treating complex diseases like cancer [13].…”

“…Lipid nanoparticles (LNPs) can be used to encapsulate these agents, enhancing their delivery directly to tumor cells while minimizing exposure to healthy tissues. Among these, microtubule inhibitors, like paclitaxel [15][16][17] and docetaxel [18][19][20][21], interfere with cell division, making them potent anticancer agents. Topoisomerase inhibitors such as etoposide [22] and 10-hydroxycamptothecin (HCPT) [23] disrupt DNA replication, essential for cancer cell proliferation.…”

The protective effects of baicalin for respiratory diseases: an update and future perspectives

“…BA has been extensively reported to treat respiratory diseases ( Deng et al, 2022 ; Ju et al, 2022 ; Li et al, 2022 ). However, the widespread use of BA is still a challenge due to its low solubility and poor bioavailability ( Haider et al, 2018 ; Pramual et al, 2022 ). And the molecular mechanism of BA in treating respiratory diseases has yet to be reported based on a summary of reliable evidence.…”

Polylactide-Based Materials: Synthesis and Biomedical Applications

“…The size of drug-loaded NPs ranges from 19 to 27 nm, and its highest loading is for NPs built from copolymers with shorter hydrophobic blocks, which is related to the low hydrophobicity of the drug. In addition, hybrid NPs composed of PLGA and a lipid block for the delivery of paclitaxel against lung cancer cells was proposed by Lirdprapamongkol et al [ 2 ]. The self-assembled NPs were uniform, with a size of around 100 nm and a negative charge on their surface.…”