For the first time, an overview of dendrimers in combination with natural products and analogues as anti-cancer agents is presented. This reflects the development of drug delivery systems, such as dendrimers, to tackle cancers. The most significant advantages of using dendrimers in nanomedicine are their high biocompatibility, good water solubility, and their entry - with or without encapsulated, complexed or conjugated drugs - through an endocytosis process. This strategy has accelerated over the years in order to develop nanosystems as nanocarriers, to decrease the intrinsic toxicity of anti-cancer agents, to decrease the drug side effects, to increase the efficacy of the treatment, and consequently to improve patient compliance.
The main objective of nanomedicine research is the development of nanoparticles as drug delivery systems or drugs per se to tackle diseases as cancer, which are a leading cause of death with developed nations. Targeted treatments against solid tumors generally lead to dramatic regressions, but, unfortunately, the responses are often short-lived due to resistant cancer cells. In addition, one of the major challenges of combination drug therapy (called "cocktail") is the crucial optimization of different drug parameters. This issue can be solved using combination nanotherapy. Nanoparticles developed in oncology based on combination nanotherapy are either (a) those designed to combat multidrug resistance or (b) those used to circumvent resistance to clinical cancer drugs. This review provides an overview of the different nanoparticles currently used in clinical treatments in oncology. We analyze in detail the development of combinatorial nanoparticles including dendrimers for dual drug delivery via two strategic approaches: (a) use of chemotherapeutics and chemosensitizers to combat multidrug resistance and (b) use of multiple cytotoxic drugs. Finally, in this review, we discuss the challenges, clinical outlook, and perspectives of the nanoparticle-based combination therapy in cancer.
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