One-Pot Preparation of Ultra-Small Lipid-Polymer Nanoparticles Loaded with Cis-Platinum to Combat Lung Cancer

Abstract

The cis-platinum (CDDP) is a first line chemotherapeutics drugs to combat lung cancer. However, its efficacy is largely limited due to the off-target delivery and multidrug resistance (MDR) upon in vivo applications. In order to solve this problem, here in our study, we prepared ultra-small lipidpolymer nanoparticles (USLPNPs) using one-pot method and to load CDDP (USLPNPs-CDDP) for the effective lung cancer therapy. Our results showed that the size of USLPNPs-CDDP was 20 nm and the stability of this platform was high. The sustained drug release afforded the long-lasting administration of CDDP to treat cancers. Most importantly, the USLPNPs-CDDP was able to bypass the CDDP resistance of A549/CDDP cells, which resulted in better anticancer benefits as compared to free CDDP both in vitro and in vivo.

Lipid Nanoparticles in Lung Cancer Therapy

“…Topoisomerase inhibitors such as etoposide [22] and 10-hydroxycamptothecin (HCPT) [23] disrupt DNA replication, essential for cancer cell proliferation. Antimetabolites, including gemcitabine [24,25] and methotrexate [26], inhibit DNA and RNA synthesis, while alkylating agents like cisplatin [27,28] directly damage DNA. Anthracyclines (e.g., doxorubicin [29,30]) and tyrosine kinase inhibitors (e.g., erlotinib [31][32][33][34]) target enzymes and signaling pathways critical for tumor growth.…”

“…Transitioning into alkylating agents, cisplatin/ultra-small lipid-polymer nanoparticles loaded with cis-platinum (USLPNPs-CDDP) were synthesized using a one-pot method to address lung cancer therapy, with a focus on overcoming drug resistance in A549/CDDP cells. These nanoparticles showed enhanced anticancer benefits and the ability to bypass drug resistance mechanisms compared to free cis-platinum, suggesting a promising advancement in treating resistant forms of lung cancer [27].…”

“…This compilation highlights the diversity in design and application of lipid nanotechnologies aimed at enhancing efficacy and specificity of cancer therapies. Pulmonary surfactant mimetic lipid vesicles Paclitaxel Chemotherapy [15] Poly(lactic-co-glycolic acid) (PLGA)-Lipid Hybrid Paclitaxel Chemotherapy [16] Nanostructured lipid carriers (NLC) Paclitaxel and Doxorubicin Combination Chemotherapy [17] Lipid-based nanoemulsion Docetaxel Chemotherapy [18] Nanostructured lipid carriers (NLC) Celecoxib and Docetaxel Chemotherapy and Anti-inflammatory [19] Epidermal Growth Factor-conjugated lipid-polymer hybrid nanoparticles Docetaxel, Resveratrol Targeted Chemotherapy [20] Transferrin-decorated protein-lipid hybrid nanoparticles Cisplatin, Docetaxel Targeted Chemotherapy [21] Lipid-polymer hybrid nanoparticles with polyvinyl alcohol Etoposide Controlled Drug Delivery [22] Polyethylene glycol-modified nanostructured lipid carriers 10-Hydroxycamptothecin Enhanced Anti-tumor Effect [23] Mannosylated solid lipid nanoparticles Gemcitabine Targeted Chemotherapy [24] Chitosan-coated solid lipid nanoparticles Methotrexate Interventional Delivery for Lung Cancer [26] Ultra-small lipid-polymer nanoparticles Cis-Platinum Targeted Chemotherapy for Lung Cancer [27] Post-bombesin-and pre-bombesin-decorated nanostructured lipid carriers…”

“…Overcoming Drug Resistance: LNPs such as paclitaxel-encapsulated PLGA-lipid hybrids and other innovative designs have targeted specific cancer cell characteristics and mechanisms, enhancing antitumor ability and overcoming resistance [21,27,35,37,48,50,52,71].…”