A landscape of recent advances in lipid nanoparticles and their translational potential for the treatment of solid tumors.

Lipid nanoparticles (LNPs) are biocompatible drug delivery systems that have found numerous applications in medicine. Their versatile nature enables the encapsulation and targeting of various types of medically relevant molecular cargo, including oligonucleotides, proteins, and small molecules for the treatment of diseases, such as cancer. Cancers that form solid tumors are particularly relevant for LNP-based therapeutics due to the enhanced permeation and retention effect that allows nanoparticles to accumulate within the tumor tissue. Additionally, LNPs can be formulated for both locoregional and systemic delivery depending on the tumor type and stage. To date, LNPs have been used extensively in the clinic to reduce systemic toxicity and improve outcomes in cancer patients by encapsulating chemotherapeutic drugs. Next-generation lipid nanoparticles are currently being developed to expand their use in gene therapy and immunotherapy, as well as to enable the co-encapsulation of multiple drugs in a single system. Other developments include the design of targeted LNPs to specific cells and tissues, and triggerable release systems to control cargo delivery at the tumor site. This review paper highlights recent developments in LNP drug delivery formulations and focuses on the treatment of solid tumors, while also discussing some of their current translational limitations and potential opportunities in the field.

One-Step Synthesis of Nanoliposomal Copper Diethyldithiocarbamate and Its Assessment for Cancer Therapy.

The metal complex copper diethyldithiocarbamate (CuET) induces cancer cell death by inhibiting protein degradation and induces proteotoxic stress, making CuET a promising cancer therapeutic. However, no clinical formulation of CuET exists to date as the drug is insoluble in water and exhibits poor bioavailability. To develop a scalable formulation, nanoliposomal (LP) CuET was synthesized using ethanol injection as a facile one-step method that is suitable for large-scale manufacturing. The nanoparticles are monodispersed, colloidally stable, and approximately 100 nm in diameter with an encapsulation efficiency of over 80%. LP-CuET demonstrates excellent stability in plasma, minimal size change, and little drug release after six-month storage at various temperatures. Additionally, melanoma cell lines exhibit significant sensitivity to LP-CuET and cellular uptake occurs predominantly through endocytosis in YUMM 1.7 cancer cells. Intracellular drug delivery is mediated by vesicle acidification with more nanoparticles being internalized by melanoma cells compared with RAW 264.7 macrophages. Additionally, the nanoparticles preferentially accumulate in YUMM 1.7 tumors where they induce cancer cell death in vivo. The development and characterization of a stable and scalable CuET formulation illustrated in this study fulfils the requirements needed for a potent clinical grade formulation.