[Construction and Anti-tumor Effect Evaluation of a Dual-Responsive Hyaluronic Acid Carbon Quantum Dot-Gelatin Nano-Drug Delivery System].

Abstract

OBJECTIVE:

To construct a pH and matrix metalloproteinase (MMP) dual-responsive nano drug delivery system with adjustable particle size so as to synergistically enhance the retention and penetration of chemotherapeutic drugs in tumor tissues and improve tumor treatment effect.

METHODS:

Hyaluronic acid (HA) carbon quantum dots (CD) coupled with gelatin nanoparticle (GNP) were constructed, and were connected with doxorubicin (DOX), a chemotherapeutic drug, through pH-sensitive imine to produce GNP@HA-CD-DOX nanoparticles. The changes of particle size, drug release behavior, hemocompatibility, cell uptake and deep penetration of tumor spheroids, in vivo tumor targeting and therapeutic effect were analyzed.

RESULTS:

GNP@HA-CD-DOX nanoparticles had a particle size of (162.93±2.55) nm, which could be degraded to release HA-CD-DOX with a particle size of about 40 nm under the treatment of MMP. The drug loading of DOX was (4.94±0.22)%. DOX was released in the tumor microenvironment and lysosomes in response to the low pH. No obvious hemolysis was observed in GNP@HA-CD-DOX. GNP@HA-CD-DOX showed a reduction in particle size after co-incubation with MMP-2. The MMP-sensitive GNP@HA-CD-DOX had significantly improved cell uptake and better deep penetration in tumor spheres. GNP@HA-CD-DOX displayed better distribution in tumor and anti-tumor ability in tumor-bearing mice compared with the small particle size HA-CD-DOX group. In addition, it has better safety.

CONCLUSION:

The pH and MMP dual-sensitive nano-tech drug delivery system with adjustable particle sizes synergistically enhances the retention and deep penetration of drugs in tumors as well as the anti-tumor effect, suggesting new approaches to tumor treatment.

• Authors: Man Li, Jian-Ping Li, Ya-Shi Wang, Qin He
• Journal: Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition (Sichuan Da Xue Xue Bao Yi Xue Ban) Vol. 52 Issue 4 Pg. 577-584 (Jul 2021) ISSN: 1672-173X [Print] China
• PMID: 34323034 (Publication Type: Journal Article)
• Copyright: Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).

Chemical References

• Carbon
• Doxorubicin
• Gelatin
• Hyaluronic Acid

Topics

• Animals
• Carbon
• Doxorubicin
• Drug Delivery Systems
• Gelatin
• Hyaluronic Acid
• Mice
• Nanoparticles
• Quantum Dots