Lipid-like Carbon-Dot Liposomes for Enhanced Drug Delivery and Membrane Fluidity Modulation in the Treatment of Metastatic Triple-Negative Breast Cancer

Abstract

Cancer metastasis remains a major clinical challenge, leading to discouraging treatment outcomes and over 90% of cancer-related mortality. In this study, lipid-like carbon dots (LCDs) are designed to self-assemble into liposome-like structures, namely carbon-dot liposomes (CDsomes), serving as a multifunctional drug carrier for anticancer and anti-metastasis therapy in highly invasive triple-negative breast cancer (TNBC). The amphiphilic nature of CDsomes enables efficient fusion with TNBC cell membranes, facilitating drug delivery while reducing membrane fluidity. This modulation significantly suppresses TNBC cell invasion, migration, and metastasis both in vitro and in vivo. The unilamellar structure of CDsomes allows efficient encapsulation of anticancer drugs with varying polarities, including doxorubicin (Dox), carfilzomib, docetaxel, gemcitabine, and cisplatin. CDsomes also promote tumor penetration and Dox accumulation through the enhanced permeability and retention effect, along with their inherent elastic and lipophilic properties. Consequently, Dox-loaded CDsomes (Dox@CDsomes) exhibit superior antitumor and anti-metastatic efficacy and improved survival rates compared to free Dox in an orthotopic TNBC model while ameliorating systemic toxicity. Notably, Dox@CDsomes achieve therapeutic outcomes comparable to commercial liposomal Dox (Doxil) while extending survival rates by 20%. These findings highlight CDsomes-mediated membrane fluidity modulation as a promising therapeutic strategy for metastasis suppression, offering new avenues in multimodal cancer therapies.