Combined cancer therapeutics—Tackling the complexity of the tumor microenvironment

Abstract

Cancer treatment has yet to find a “silver bullet” capable of selectively and effectively kill tumor cells without damaging healthy cells. Nanomedicine is a promising field that can combine several moieties in one system to produce a multifaceted nanoplatform. The tumor microenvironment (TME) is considered responsible for the ineffectiveness of cancer therapeutics and the difficulty in the translation from the bench to bed side of novel nanomedicines. A promising approach is the use of combinatorial therapies targeting the TME with the use of stimuli‐responsive nanomaterials which would increase tumor targeting. Contemporary combined strategies for TME‐targeting nanoformulations are based on the application of external stimuli therapies, such as photothermy, hyperthermia or ultrasounds, in combination with stimuli‐responsive nanoparticles containing a core, usually composed by metal oxides or graphene, and a biocompatible stimuli‐responsive coating layer that could also contain tumor targeting moieties and a chemotherapeutic agent to enhance the therapeutic efficacy. The obstacles that nanotherapeutics must overcome in the TME to accomplish an effective therapeutic cargo delivery and the proposed strategies for improved nanotherapeutics will be reviewed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

Tumor Microenvironment-Responsive Shell/Core Composite Nanoparticles for Enhanced Stability and Antitumor Efficiency Based on a pH-Triggered Charge-Reversal Mechanism

“…The tumor microenvironment (TME) presents several distinguishable pathological features such as mildly acidic pH, hypoxia, high level of reactive oxygen species, and overexpression of specific enzymes, which have been exploited as stimuli to induce dePEGylation [ 5 , 6 , 7 ]. To sum up, PEGylation/dePEGylation strategies involve chemical and physical approaches.…”

Exploring RAB11A Pathway to Hinder Chronic Myeloid Leukemia-Induced Angiogenesis In Vivo

“…Gold nanoparticles (AuNPs) have become significant players in the field of nano-medicine [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Due to their simple manufacture, high surface area, and distinctive physical and chemical properties, these nanoparticles are suited for use in a wide range of applications, including diagnosis, therapy, and imaging of various diseases [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

“…Gold nanoparticles (AuNPs) have become significant players in the field of nano-medicine [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Due to their simple manufacture, high surface area, and distinctive physical and chemical properties, these nanoparticles are suited for use in a wide range of applications, including diagnosis, therapy, and imaging of various diseases [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The surface plasmon resonance (SPR) by itself, one of the physical characteristics that confers exceptional light-to-heat conversion efficiencies, contributes to the AuNPs use as photothermal agents [ 31 , 32 , 33 , 34 , 36 , 37 , 38 ].…”

“…Due to their simple manufacture, high surface area, and distinctive physical and chemical properties, these nanoparticles are suited for use in a wide range of applications, including diagnosis, therapy, and imaging of various diseases [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The surface plasmon resonance (SPR) by itself, one of the physical characteristics that confers exceptional light-to-heat conversion efficiencies, contributes to the AuNPs use as photothermal agents [ 31 , 32 , 33 , 34 , 36 , 37 , 38 ]. Moreover, a wide range of biomolecules, including targeting and silencing moieties, dyes, or chemotherapeutic medicines, can easily be functionalized onto the surface of AuNPs, enabling the use of these particles for therapeutic, imaging, targeting applications, and combined therapies [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

A Nanosized Codelivery System Based on Intracellular Stimuli-Triggered Dual-Drug Release for Multilevel Chemotherapy Amplification in Drug-Resistant Breast Cancer

“…In general, some insoluble chemotherapeutics can be encapsulated into the inner lipophilic portion of PNPs via hydrophobic interactions, while other active compounds can be adsorbed, bound, or conjugated to the surfacefunctionalized hydrophilic part [30]. Moreover, inspired by some specific hallmarks in the tumor cells, such as reduced pH value (6.2-6.9), overproduced glutathione (GSH, 2-20 mM), and elevated temperature (40-42 • C) [31], multifarious stimuli-responsive PNPs have been developed for enhanced anticancer efficiency by controlling drug release rapidly at tumor sites [32]. Keeping all this in mind, we designed and prepared intracellular stimuli-triggered functionalized hybrid PNPs for co-loading PTX and QU (Scheme 1) which consist of PTX/polyethyleneimine-tocopherol hydrogen succinate-dithioglycollic acid PNPs (PTX/PEI-TOS-SS PNPs, PTX/PTS PNPs) and hyaluronic acid-QU (HA-QU, HQ) conjugates.…”