Nanocarriers address intracellular barriers for efficient drug delivery, overcoming drug resistance, subcellular targeting and controlled release

The cellular barriers are major bottlenecks for bioactive compounds entering into cells to accomplish their biological functions, which limits their biomedical applications. Nanocarriers have demonstrated high potential and benefits for encapsulating bioactive compounds and efficiently delivering them into target cells by overcoming a cascade of intracellular barriers to achieve desirable therapeutic and diagnostic effects. In this review, we introduce the cellular barriers ahead of drug delivery and nanocarriers, as well as summarize recent advances and strategies of nanocarriers for increasing internalization with cells, promoting intracellular trafficking, overcoming drug resistance, targeting subcellular locations and controlled drug release. Lastly, the future perspectives of nanocarriers for intracellular drug delivery are discussed, which mainly focus on potential challenges and future directions. Our review presents an overview of intracellular drug delivery by nanocarriers, which may encourage the future development of nanocarriers for efficient and precision drug delivery into a wide range of cells and subcellular targets.