Objective: To review selected recent studies on the therapeutic applications of nanoparticles and nanoparticle-conjugated antimicrobials as new therapeutic alternatives for a variety of intracellular infections.
 Data Sources: Recent published papers on nanoparticles and intracellular infections, including bacterial, viral, and parasitic diseases in humans. The PubMed database was used as the main source. Publicly available papers were retrieved.
 Summary of Contents: Therapeutic failure in intracellular infections is a challenging clinical problem. Antibiotics, anti-parasitics, antivirals, and other drugs might not reach effective levels in intracellular compartments; these agents in high doses might become toxic and may show undesirable effects. Researchers have been looking for alternative strategies for antimicrobials to reach intracellular spaces. The development of novel drugs and release mechanisms is currently a research priority in infectious diseases. With this background, new approaches such as those based on nanotechnology, including the fabrication of drug nanocarriers, are of increasing interest to researchers and clinicians. The goal for nanocarriers is to provide controlled release of drugs into cellular compartments with high selectivity, higher efficiency, better therapeutic outcomes, less toxicity, and more rational dosing schemes compared to traditional ones. Biocompatibility of nanocarriers may ensure affinity to the reticuloendothelial and immunological systems, which might facilitate drug delivery into intracellular compartments.
 Conclusion: Nanoparticle systems have great potential in infectious diseases, particularly in difficult-to-treat infections, such as those caused by intracellular pathogens. These systems have been tested with several drugs, enzymes, genes, and peptides, showing long half-lives due to their hydrophilic coatings. The optimization of nanoparticle-based drug delivery systems has improved our understanding of the different mechanisms underlying biological interactions and the engineering of even more complex nanoparticles.
 Keywords: Nanoparticles, intracellular infections, novel therapeutics.
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