<p>pH-Responsive Fluorescence Enhanced Nanogel for Targeted Delivery of AUR and CDDP Against Breast Cancer</p>

Abstract

Introduction Auraptene (AUR), a natural bioactive prenyloxy coumarin, is a highly pleiotropic molecule that can bind to the MT1 receptor and can effectively reduce the proliferation and migration of breast cancer cells. Cisplatin (CDDP), as the first synthetic platinum-based anticancer drug, is widely used in the clinic due to its definite mechanism and therapeutic effect on diverse tumors. However, both of AUR and CDDP exhibit some disadvantages when used alone, including poor solubility, low bioavailability, lack of selectivity and systemic toxicity when they are used singly. Methods Therefore, the biodegradable materials hyaluronic acid (HA) and β-cyclodextrin derivative (mono-(6-amino-mono-6-deoxy)-β-CD, CD) were employed as carriers to load AUR and CDDP to form nanogel ( CDDP HA-CD@AUR) capable of dual-targeted delivery and synergistic therapy for breast cancer and cell imaging. Results With the help of the CDDP-crosslinked CD-loaded structure, the newly synthesized nanogel exhibited excellent physiological stability and fluorescence effects. The release of AUR and CDDP was affected by the pH value, which was beneficial to the selective release in the tumor microenvironment. Cell experiments in vitro demonstrated that the nanogel could be selectively internalized by MCF-7 cells and exhibited low cytotoxicity to HK-2 cells. Antitumor experiments in vivo showed that the nanogel have better antitumor effects and lower systemic toxicity. Conclusion Based on these, the nanogel loaded with AUR and CDDP have the potential for targeted delivery against breast cancer.

Tailoring Hyaluronic Acid Hydrogels for Biomedical Applications

“…Cancer treatment [ 186] Nanogel HA Paclitaxel Enzyme-sensitive targeting Breast cancer treatment [ 187] Nanogel HA and 𝛽-CD derivative Auraptene and cisplatin pH-responsive, targeted delivery Synergistic therapy for breast cancer and cell imaging [ 188] Nanogel Poly (ethylene glycol) conjugated HA Cytochrome C Hypoxia response CD44 mediated tumor targeting [ 189] Nanogel Pluronic L61 linked HA Acid-sensitive capacity Cancer treatment [ 190] Nanogel HA, cisplatin, cancer cell membrane…”

Hyaluronic Acid-Based Nanomaterials Applied to Cancer: Where Are We Now?

“…Additionally, it demonstrated a selective cytotoxicity to breast cancer cells compared to normal ones, which is a great indicator of biosafety. This is enhanced by the in vivo results, since the nanogel was able to reduce tumor volume while showing reduced systemic toxicity [ 52 ]. Nanogel application in theranostics has been demonstrated by Pan et al [ 53 ].…”

Strategic Design of Intelligent-Responsive Nanogel Carriers for Cancer Therapy

“…It is known that there are abundant enzymes, including proteolytic enzymes, lipase, lysosomal enzymes, matrix metalloproteinases, and hyaluronidase. The enzyme possesses efficient and highly specific catalysts, which have inspired various enzyme-responsive nanogels for drug/protein delivery and triggered release in tumor site. − For example, hyaluronic acid (HA) could intrinsic target toward CD44-overexpressed tumor cells. , It can be degraded when triggered by extracellular overexpressed hyaluronidases (HAase) in tumor tissue. As shown in Figure , Wang et al reported P-5m peptide encapsulated enzyme-responsive nanogels based on PNIPAM prepared by free radical precipitation polymerization .…”

“…29−31 For example, hyaluronic acid (HA) could intrinsic target toward CD44-overexpressed tumor cells. 124,125 It can be degraded when triggered by extracellular overexpressed hyaluronidases (HAase) in tumor tissue. As shown in Figure 5, Wang et al reported P-5m peptide encapsulated enzyme-responsive nanogels based on PNIPAM prepared by free radical precipitation polymerization.…”