Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

Abstract

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

Chemotherapeutic Drug Based Metal–Organic Particles for Microvesicle‐Mediated Deep Penetration and Programmable pH/NIR/Hypoxia Activated Cancer Photochemotherapy

“…), thus enhancing the antitumoral efficiency 1, 2. Various stimuli‐responsive DDSs have been designed for cancer treatment, such as pH‐triggered nanocomposites,3, 4 GSH or temperature‐responsive nanoparticles,5, 6 and porous‐based smart nanoparticles 7, 8, 9. However, such DDS systems are still unsatisfactory and suffer from various shortcomings, including complicated synthetic processes and low repeatability due to complex designs, limited drug payloads, nonspecific drug leakage and nondegradable compositions 3, 5, 9.…”

“…Various stimuli‐responsive DDSs have been designed for cancer treatment, such as pH‐triggered nanocomposites,3, 4 GSH or temperature‐responsive nanoparticles,5, 6 and porous‐based smart nanoparticles 7, 8, 9. However, such DDS systems are still unsatisfactory and suffer from various shortcomings, including complicated synthetic processes and low repeatability due to complex designs, limited drug payloads, nonspecific drug leakage and nondegradable compositions 3, 5, 9. Thus, developing a novel stimuli‐responsive DDS with excellent biocompatibility, high drug payload, deep penetration into solid tumors, minimized nonspecific drug activation, and good repeatability with a simple strategy is urgently needed for cancer treatment.…”

“…Some MOF structures that exhibit extremely interesting properties, such as a highly porous structure with pore sizes from 0.4 to 6 nm and a very large surface area, are ideal structures for separation, catalysis, gas‐storage, and exceptional delivery applications 10, 11. However, most previously published MOF structures (such as Cr‐, Co‐, and Ni‐based MOFs) are not suitable for bioapplications due to their disadvantages including biological toxicity and bioinstability, as hydrolysis or decomposition even can occur in the presence of moisture 9, 10, 11, 12, 13, 14. Recently, nanoscale metal–organic particles, which have been designed for biomedicine applications by judiciously selecting inorganic and organic building blocks, have shown great potential for drug delivery, photodynamic therapy (PDT), photothermal therapy, nucleic acid delivery, and biomedical imaging 15, 16, 17.…”

Controlling the morphology of copolymeric vectors for next generation nanomedicine

“…Polymeric NVs, in particular, are amenable to the incorporation of stimuli responsive components through blending with chemically responsive structural units [39]. Structures that can undergo morphogenic transformation via enzymatic degradation, pHinduced charge reversal, sol-gel transitions, redox sensitive bond cleavage, photo-induced cleavage or isomerization can be utilised to target biological environments that display the requisite parameters (or in the case of photosensitivity introduce an external stimulus) [40][41][42]. Such changes in the morphological properties of NVs would facilitate a concomitant activation or release of functional cargo in order to address the particular diseased tissue and, as such, have great clinical potential [43].…”

Enzyme/pH-sensitive dendritic polymer-DOX conjugate for cancer treatment

“…. was no profound aggregation of dendritic conjugate in PBS with 50% FBS and dendritic conjugate exhibited much favorable serum stability for 24 h. The excellent stability of dendritic conjugate might be ascribed to the overall negative surface charge of dendritic conjugate that could minimize the interaction between dendritic conjugate and plasma proteins and prevent drug leakage during blood circulation. Moreover, the stability may prolong the blood circulation half-life and improve the efficiency in drug delivery into tumor tissues in vivo [37][38][39].…”