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The therapeutic and diagnostic effects of nanoparticles highly depend on the efficiency of their delivery to targeted tissues, such as tumors. The size of nanoparticles, among other characteristics, plays a crucial role in determining their tissue penetration and retention. Small nanoparticles may penetrate deeper into tumor parenchyma but are poorly retained, whereas large ones are distributed around tumor blood vessels. Thus, compared to smaller individual nanoparticles, assemblies of such nanoparticles due to their larger size are favorable for prolonged blood circulation and enhanced tumor accumulation. Upon reaching the targeted tissues, nanoassemblies may dissociate at the target region and release the smaller nanoparticles, which is beneficial for their distribution at the target site and ultimate clearance. The recent emerging strategy that combines small nanoparticles into larger, biodegradable nanoassemblies has been demonstrated by several groups. This review summarizes a variety of chemical and structural designs for constructing stimuli-responsive disintegrable nanoassemblies as well as their different disassembly routes. These nanoassemblies have been applied as demonstrators in the fields of cancer therapy, antibacterial infection, ischemic stroke recovery, bioimaging, and diagnostics. Finally, we summarize stimuli-responsive mechanisms and their corresponding nanomedicine designing strategies, and discuss potential challenges and barriers towards clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells., Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents., Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.

The synthesis of microcapsules consisting of DNA shells crosslinked by anti-VEGF (vascular epithelial growth factor) or anti-ATP (adenosine triphosphate) aptamers and loaded with tetramethylrhodamine-modified dextran, TMR-D, and Texas Red-modified dextran, TR-D, respectively, as fluorescence labels acting as models for drug loads, is described. The aptamer-functionalized microcapsules act as stimuli-responsive carriers for the triggered release of the fluorescent labels in the presence of the overexpressed cancer cell biomarkers VEGF or ATP. The VEGF- and ATP-responsive microcapsules are, also, loaded with the anticancer drug doxorubicin (DOX), in the form of DOX-functionalized dextran, DOX-D. The release of DOX-D from the respective microcapsules proceeds in the presence of VEGF or ATP as triggers. Preliminary cell experiments reveal that the ATP-responsive DOX-D-loaded microcapsules undergo effective endocytosis into MDA-MB-231 cancer cells. The ATP-responsive DOX-D-loaded microcapsules incorporated into the MDA-MB-231 cancer cells reveal impressive cytotoxicity as compared to normal epithelial MCF-10A breast cells (50% vs 0% cell death after 24 h, respectively). The cytotoxicity of the ATP-responsive DOX-D-loaded microcapsules toward the cancer cells is attributed to the effective unlocking of the microcapsules by overexpressed ATP, and to the subsequent release of DOX from the dextran backbone under acidic conditions present in cancer cells (pH = 6.2). [ABSTRACT FROM AUTHOR]

Adenosine triphosphate (ATP)–responsive DNA‐based microcapsules loaded with the chemotherapeutic doxorubicin drug are synthesized and incorporated into cancer cells. I. Willner and co‐workers find, on page 4262, that over‐expressed ATP in cancer cells dissociates the microcapsules and releases the drug, resulting in selective cytotoxicity toward cancer cells. [ABSTRACT FROM AUTHOR]

Degradable and light-addressable silica capsules have been prepared on the basis of CaCO3 template particles. It was possible to load these capsules with an array of molecules such as anticancer drugs (doxorubicin), proteins (bovine serum albumin), and nucleic acids (mRNA encoding green fluorescent protein). In vitro degradation and release of these molecules was demonstrated and quantitatively compared with several kinds of polyelectrolyte multilayer capsules as examples of other delivery vehicles. The data suggests hydrolysis as a mechanism involved in intracellular degradation of silica capsules. Photothermal heating (by integrating plasmonic nanoparticles in the silica shell) was further used to induce remote molecular release. [ABSTRACT FROM AUTHOR]