Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

Introduction: Cell penetrating peptides (CPPs) known as protein translocation domains (PTD), membrane translocating sequences (MTS) or Trojan peptides (TP) are able to cross biological membranes without clear toxicity using different mechanisms, and facilitate the intracellular delivery of a variety of bioactive cargos. CPPs could overcome some limitations of drug delivery and combat resistant strains against a broad range of diseases. Despite delivery of different therapeutic molecules by CPPs, they lack cell specificity and have a short duration of action. These limitations led to design of combined cargo delivery systems and subsequently improvement of their clinical applications. Areas covered: This review covers all our studies and other researchers in different aspects of CPPs such as classification, uptake mechanisms and biomedical applications. Expert opinion: Due to low cytotoxicity of CPPs as compared to other carriers and final degradation to amino acids, they are suitable for preclinical and clinical studies. Generally, the efficiency of CPPs was suitable to penetrate the cell membrane and deliver different cargos to specific intracellular sites. However, no CPP-based therapeutic approach has approved by FDA, yet; because there are some disadvantages for CPPs including short half-life in blood, and non-specific CPP-mediated delivery to normal tissue. Thus, some methods were used to develop the functions of CPPs in vitro and in vivo including the augmentation of cell specificity by activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, incorporation of CPPs into multifunctional dendrimeric or liposomal nanocarriers to improve selectivity and efficiency especially in tumor cells.