Tumor-microenvironment double-responsive shrinkable nanoparticles fabricated via facile assembly of laponite with a bioactive oligosaccharide for anticancer therapy

The application of nanoparticle-based delivery systems is limited by uncontrolled drug release, limited tumor penetration, and poor stability. To solve these problems, a tumor microenvironment pH and enzyme double -responsive shrinkable nanoparticle was developed in this study and defined as LDC (the complex of laponite (LP), doxorubicin (DOX), and chito-oligosaccharides (COS)). LDC has a 100 nm size and contains the anticancer medication DOX, which is stable in serum-containing aqueous solutions and can efficiently accumulate in tumors in vivo. The tumor extracellular matrix is in rich of lysozymes, which can degrade COS and release smaller DOX-containing nanoparticles, making LDC shrink from the initial 100 nm into 30 nm (in diameter) to facilitate the drug to penetrate deeply into the tumor tissue. Furthermore, after being taken up by tumor cells, the acidic and enzymatic cellular microenvironment triggers quick DOX release and rapid killing of cancer cells. LDC exhibits hardly any in vivo toxicity to mice's major organs. These results demonstrated that LDC can ensure a system-atically tumor-targeting controlled drug release, deep tumor penetration, and stability in circulation to avoid damages on healthy organs/tissues, demonstrating its potential as an effective thereaputic delivery approach for cancer treatment.

Automated summary

In this study, a tumor microenvironment pH and enzyme double-responsive shrinkable nanoparticle, called LDC, was developed to address the issues of uncontrolled drug release, limited tumor penetration, and poor stability in nanoparticle-based delivery systems. LDC has a size of 100 nm and contains stable anticancer medication DOX, which efficiently accumulates in tumors. The presence of lysozymes in the tumor extracellular matrix degrades COS and releases smaller DOX-containing nanoparticles, causing LDC to shrink to 30 nm and facilitate deep tumor penetration.