Facile Chemical Strategy to Hydrophobically Modify Solid Nanoparticles Using Inverted Micelle-Based Multicapsule for Efficient Intracellular Delivery

Theranostic nanoparticles have incredible potential for biomedical applications by enabling visual confirmation of therapeutic efficacy. Numerous issues challenge their clinical translation and are primarily related to the complex chemistry and scalability of synthesizing Nanoparticles. We report a 2-step chemical strategy for high-throughput intracellular delivery of organic and inorganic solid nanoparticles. This process takes an additional step beyond hydrophobic surface modification facilitated by inverted micelle transfer, toward the packing of multiple solid nanoparticles into a soft-shelled lipid capsule, termed the Nano-multicapsule (NMC). This technique is high yielding and does not require the complex purification steps in anaerobic/hydrophobic reactions for hydrophobic modification. To demonstrate the efficacy across different material compositions, we separately entrapped ∼10 nm gold and carbon nanoparticles (AuNP and CNP) within inverted micelles, and subsequently NMCs, then quantified their internalization in a human breast cancer cell line. For encapsulated AuNPs (NMC-AuNP), we confirmed greater cellular internalization of gold through ICP-OES and TEM analyses. Raman spectroscopic analysis of cells treated with encapsulated CNPs (NMC-CNP) also exhibited high degrees of uptake with apparent intracellular localization as opposed to free CNP treatment.