Recent Advances and Impact of Chemotherapeutic and Antiangiogenic Nanoformulations for Combination Cancer Therapy.

Amit Kumar Rajora,Jessica M. Rosenholm,Divyashree Ravishankar,Hongbo Zhang

doi:10.3390/pharmaceutics12060592

Amit Kumar Rajora, Jessica M. Rosenholm + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics12060592

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Journal: Pharmaceutics	Publication Date: Jun 25, 2020
Citations: 26	License type: CC BY 4.0

Affiliation: Åbo Akademi University, University of Turku

Abstract

Traditional chemotherapy, along with antiangiogenesis drugs (combination cancer therapy), has shown reduced tumor recurrence and improved antitumor effects, as tumor growth and metastasis are often dependent on tumor vascularization. However, the effect of combination chemotherapy, including synergism and additive and even antagonism effects, depends on drug combinations in an optimized ratio. Hence, nanoformulations are ideal, demonstrating a great potential for the combination therapy of chemo-antiangiogenesis for cancer. The rationale for designing various nanocarriers for combination therapy is derived from organic (polymer, lipid), inorganic, or hybrid materials. In particular, hybrid nanocarriers that consist of more than one material construct provide flexibility for different modes of entrapment within the same carrier—e.g., physical adsorption, encapsulation, and chemical conjugation strategies. These multifunctional nanocarriers can thus be used to co-deliver chemo- and antiangiogenesis drugs with tunable drug release at target sites. Hence, this review attempts to survey the most recent advances in nanoformulations and their impact on cancer treatment in a combined regimen—i.e., conventional cytotoxic and antiangiogenesis agents. The mechanisms and site-specific co-delivery strategies are also discussed herein, along with future prospects.

Highlights

Cancer is one of the leading causes of death, and its treatment remains one of the most severe challenges worldwide
These nanosized drug delivery systems have been found to be promising in the field of cancer therapy due to their improved pharmacokinetic (PK) profiles over low molecular weight drugs [50,51,52]
The results showed that the release rate of Dox was much slower than that of combretastatin A4 (CA4) in vitro

Summary

Introduction

Cancer is one of the leading causes of death, and its treatment remains one of the most severe challenges worldwide. The inhibition of tumor angiogenesis by interfering with the VEGF pathway either by the direct inhibition of VEGF (e.g., Bevacizumab) or by the inhibition of autophosphorylation of VEGFR2 (e.g., sunitinib, sorafenib) has become a therapeutic target for cancer therapy and other angiogenesis-dependent diseases [25,26,27] This approach has been shown to contract the tumor size and prevent its further growth. The high efficacy and increased tumor selectivity are due to their prolonged circulation time and selective accumulation into tumor tissue through the enhanced permeability and retention (EPR) effect [46,47,48,49] These nanosized drug delivery systems have been found to be promising in the field of cancer therapy due to their improved pharmacokinetic (PK) profiles over low molecular weight drugs [50,51,52]. Spirmoailcahrelys,fdoirfftehreenimt applpemroeancthaetsiofnorotfhtewimo dplreumgsenintaationnanoofctawroriedrruarges dinepainctaendoicnarFriiegruarere2d. eHpeicntceed, tniphnaointsFeorinfgeotvuirairmelewtuh2l.eaextrHiapopelnonesruceoetsif,coatshnnoitgsifocnarinenavgnceiorerefwoasrenmaedxrucaphlnlaotatirinaoendsngspoioornegfgseaoenninnitctigscdafrruneutcsgueerraceoracmpnhrdboaisannpnadettciioaptsnnrgesfosifoerognrthetmsneiofpcuroedttureeruffnegteicpactlroivotmhespebcreioancmptasetbiuoifnotniarcstsitfohoonerf cmaonrceeretfhfeecrtaivpey.combination cancer therapy

Encapsulation Method

Physical encapsulation and chemical conjugation a

Findings

Lipid Based Nanoformulations