RESUMO
Cytosolic delivery of bioactive agents has exhibited great potential to cure undruggable targets and diseases. Because biological cell membranes are a natural barrier for living cells, efficient delivery methods are required to transfer bioactive and therapeutic agents into the cytosol. Various strategies that do not require cell invasive and harmful processes, such as endosomal escape, cell-penetrating peptides, stimuli-sensitive delivery, and fusogenic liposomes, have been developed for cytosolic delivery. Nanoparticles can easily display functionalization ligands on their surfaces, enabling many bio-applications for cytosolic delivery of various cargo, including genes, proteins, and small-molecule drugs. Cytosolic delivery uses nanoparticle-based delivery systems to avoid degradation of proteins and keep the functionality of other bioactive molecules, and functionalization of nanoparticle-based delivery vehicles imparts a specific targeting ability. With these advantages, nanomedicines have been used for organelle-specific tagging, vaccine delivery for enhanced immunotherapy, and intracellular delivery of proteins and genes. Optimization of the size, surface charges, specific targeting ability, and composition of nanoparticles is needed for various cargos and target cells. Toxicity issues with the nanoparticle material must be managed to enable clinical use.
RESUMO
In many cases, a single mode of cancer therapy shows limited efficacy in treating complex and heterogeneous tumors. To improve cancer treatment, combining chemo-, photodynamic-, photothermal-, radio-, and immunotherapy is clinically recognized. When different therapeutic treatments are combined, they often show synergetic effects that further improve therapeutic outcomes. In this review, we introduce nanoparticle (NP)-based combination cancer therapies that use organic and inorganic NPs. Liposomes, polymers, and exosomes can be prepared with amphiphilic properties, high physical stability, and low immune response to treat cancers in a multimodal way. Inorganic NPs, including upconversion, plasmonic, and mesoporous silica NPs, have emerged as a new technology for photodynamic-, photothermal-, and immunotherapy. These NPs can simultaneously carry multiple drug molecules and deliver them efficiently to tumor tissue, as demonstrated in many studies. In addition to reviewing recent advances in organic and inorganic NPs used in combination therapy for cancers, we also discuss their rational design and the outlook for future nanomedicine development.
