Hyaluronidase-Responsive Mesoporous Silica Nanoparticles with Dual-Imaging and Dual-Target Function

Abstract

Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu3+ and Gd3+ during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu3+ and Gd3+ into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.

Mesoporous Silica Nanoparticles for Targeting Subcellular Organelles

“…Then, the acid pH of the lysosomes cleaved the citraconic anhydride and triggered the lysosomal escape and subsequent nuclear translocation, where DOX was rapidly released, inducing an apoptotic effect in the cells. Wu Z et al synthesized dual-targeted, enzyme-responsive MSNs for anticancer therapy and imaging [ 95 ]. They doped the MSNs during the synthesis with Eu 3+ and Gd 3+ for carrying out bioimaging.…”

Multi‐Targeted and On‐Demand Non‐Coding RNA Regulation Nanoplatform against Metastasis and Recurrence of Triple‐Negative Breast Cancer

“…After entering tumor cells, MTOR is subjected to lysosomal hyaluronidase-induced shell (HPU) detachment, [23,24] leading to a TAT peptide exposed nano-core, thus increasing the delivery of pa21-p205 into the nucleus of TNBC cells and BrCSCs. [25,26] Considering the advanced features mentioned above, our MTOR offers a new strategy against metastasis and recurrence of TNBC.…”

pH-Responsive Drug Delivery and Imaging Study of Hybrid Mesoporous Silica Nanoparticles

“…To achieve the release of the drug in the targeted diseased tissues, several surface-functionalized coatings as gatekeepers are modified onto the MSN carriers to block the drug in the pore channels [ 19 , 20 , 21 , 22 ]. Various types of stimuli could be used to open the gatekeepers, such as pH [ 23 , 24 ], enzymes [ 25 ], redox [ 26 , 27 ], light [ 28 ], ultrasound [ 29 ], and temperature [ 30 ].…”