Shape Transformable Strategies for Drug Delivery

Abstract

In tumor therapy, nanodrug delivery systems have gained momentum in the last decade. However, its efficacy remains insufficient for clinical applications. The physical properties of nanoparticles, including size, shape, and surface characteristics, can strongly affect the delivery efficacy. Ironically, research on shape function is relatively scarce, although the nanoparticle shape greatly impacts their performance; for example, nanorods with a high aspect ratio (AR) achieve greater accumulation, but their penetration is relatively weak. Hence, rather than selecting a suitable AR to balance them, the strategy of a transformable AR (i.e., transformation) is ideal in this case. Nanoparticle transformation can be achieved by either internal stimuli (such as pH and enzymes) or external stimuli (such as light) spatially and temporally with precision, thereby dramatically enhancing the efficiency of drug delivery. Thus, nanoparticle transformation is becoming a promising prospect for improving cancer treatment. In this review, first, the effect of shape on drug delivery is summarized, then, the recently transformable drug delivery systems are reviewed, and finally, the future direction of shape-transformable nanoparticles in tumor therapy is discussed.

Tumor‐Microenvironment‐Responsive Nanomedicine for Enhanced Cancer Immunotherapy

“…[ 13 , 19 ] Furthermore, various drug delivery systems with adjustable physiochemical properties (e.g., size, shape, and surface parameters) or multiple functions can facilitate inhibitory or stimulatory actions to the immune system which exert synergistic effects for combined cancer immunotherapy. [ 20 ] To achieve the multifunctional ability of nanomedicines in immunotherapy, stimuli‐responsive units were usually designed and incorporated into the nanoparticles, which respond to internal stimuli, such as pH, redox potential, hypoxia, enzymes, and adenosine triphosphate (ATP) in the TME or external stimuli such as light, ultrasonic waves, X‐rays, and electrical and magnetic fields. [ 21 ] Compared with external stimuli, TME‐responsive nanomedicine exhibits the advantage that it is safe and convenient to implement without the need of outside equipment, which has attracted increasing attention in cancer immunotherapy.…”

Self‐Delivered Supramolecular Nanomedicine with Transformable Shape for Ferrocene‐Amplified Photodynamic Therapy of Breast Cancer and Bone Metastases

“…However, the specificity of pH response, slow enzymolysis, and irradiation time all restrict the transformation efficiency. [12] Therefore, the sensitivity and specificity of stimulus-responsive shape conversion combined to determine the fate of shapeswitchable nanomedicines.…”

Design of Smart Size‐, Surface‐, and Shape‐Switching Nanoparticles to Improve Therapeutic Efficacy

“…In this context, there is a need to improve our general understanding of how nanoparticles interact with various tissues and better understand the types of nanoparticle modifications that would enable improved targeting of different disease states; [ 204 ] in parallel, identifying appropriate physical and/or biological signatures of different diseases that can be leveraged via appropriate materials design to create a switchable nanoparticle specific to that disease state is also essential to enable this approach to be extended to treat diseases other than cancer, RA, and infection that have been the focus of virtually all examples in this field to‐date due to their better‐defined physical disease states. 2)Although the role of particle shape in controlling nanoparticle biodistribution and cell responses is now better understood, [ 223 ] it has not yet been clearly leveraged in the field of switchable nanoparticles into more efficient treatments. [ 234 ] Effective leveraging of particle shape switching is more technically challenging than size/charge given that there are fewer direct chemical stimuli that are useful for such switching, particularly if a switch from a sphere to a higher surface area nanoparticle is desired (as is often the case based on the shape effects described in Table 9). Exploring new self‐assembly‐based systems that can better stabilize anisotropic nanoparticle structures under disease‐relevant conditions may offer significant opportunities to better leverage the role of shape, both alone and in conjunction with the size/charge switching strategies that are already reasonably well developed. 3)The specificity of some of the transitions to particular disease sites remains a key limitation of some targeted therapies.…”