Cisplatin-Cross-Linked and Oxygen-Resupply Hyaluronic Acid-Based Nanocarriers for Chemo-photodynamic Therapy

Abstract

Tumor microenvironment (TME) is known to play a critical role in cancer progression and contributes to treatment failure or success. Herein, a versatile nanoplatform [HAFOE-Ce6/ Pt-NPs(O 2 )] with cisplatin (Pt) cross-linking, chlorin e6 (Ce6) loading, pH sensitivity, active targeting, and oxygen resupply was developed to address this problem. This nanosystem presents as a spherical shape with a small size of 175.4 ± 2.16 nm and a negative charge of −25.32 ± 3.04 mV. Hyaluronic acid (HA) as the starting material not only improved the biocompatibility of the nanosystem but also enhanced cellular uptake by targeting the CD44 receptor. Interestingly, cisplatin could serve as both a cross-linker and anticarcinogen to increase the blood stability and therapeutic performance. Additionally, the micelles disintegration and drug release could be accelerated by the cleavage of ortho ester at low pH. More importantly, the fluorocarbon inside the particles has the ability to load oxygen and in situ release oxygen at tumor regions, which greatly reduced tumor hypoxia. In vitro and in vivo results demonstrated that HAFOE-Ce6/Pt-NPs(O 2 ) could efficiently inhibit tumor growth by combined chemo-photodynamic therapy under 660 nm laser irradiation by way of oxygen sensitization, leading to a high mice survival rate (83.33%). Overall, this combined nanosystem could take advantage of TME while overcoming its disadvantages and was an efficient nanoplaform for cancer treatment.

Fluoride‐Ortho Ester Dimer‐Based pH‐Sensitive Nanoparticles for Oxygen Delivery and Enhanced Photodynamic Therapy

“…Intracellular Hypoxia Relief: To study the ability of hypoxia relief of 7F@OE-NPs and 15@OE-NPs in tumor cells, the hypoxic environment was established according to the authors' previous works. [51] After that, hypoxia tumor cells were cocultured with 7F@OE-NPs(O 2 ) and www.advancedsciencenews.com www.particle-journal.com 15F@OE-NPs(O 2 ) for 2 h. Next, these cells were incubated with a O 2 sensing probe [(Ru(dpp) 3 )] Cl 2 for another 30 min. Finally, cells were washed with PBS and observed by CLSM at the excitation of 463 nm and emission of 620 nm.…”

PEGA-BA@Ce6@PFCE Micelles as Oxygen Nanoshuttles for Tumor Hypoxia Relief and Enhanced Photodynamic Therapy

“…For instance, Tang [ 15 ] developed a hybrid semiconducting organosilica-based O 2 nanoeconomizer, pHPFON-NO/O 2 , to combat tumor hypoxia. Cheng [ 16 ] developed a versatile nanoplatform (HAFOE-Ce 6 /Pt-NPs(O 2 )) with rapid and controlled release of its loaded oxygen. Zhuang [ 17 ] synthesized a chitosan (CS)-capped nanosystem that could codeliver oxygen, photosensitizer, and chemotherapy drugs.…”

Hyaluronic Acid–Polyethyleneimine Nanogels for Controlled Drug Delivery in Cancer Treatment

“…13 For this reason, the polymer may act as an active targeting moiety for the intracellular delivery of anticancer drugs and represents a suitable component for the synthesis of nanocarriers. 14,15 On the other hand, LPEI is a cationic polymer widely used in the synthesis of nanocarriers for drug and gene delivery due to its unique proton-sponge effect. 16,17 The presence of amine groups in the polymer backbone enables its covalent coupling with several functionalities/biomolecules and the formation of 3D nanomatrices with a huge internal space and a soft skeleton structure.…”

“…HA is an anionic, nonsulfated glycosaminoglycan commonly used in the fabrication of biomaterials for tissue engineering, drug delivery, and imaging purposes due to its highly biodegradable, biocompatible, viscoelastic, nontoxic, and nonimmunogenic nature. , Among the biological applications, HA has been widely investigated for target therapy in cancer, thanks to its well-demonstrated affinity to CD44 (hyaluronan receptor), overexpressed on the surface of many tumor cells . For this reason, the polymer may act as an active targeting moiety for the intracellular delivery of anticancer drugs and represents a suitable component for the synthesis of nanocarriers. , On the other hand, LPEI is a cationic polymer widely used in the synthesis of nanocarriers for drug and gene delivery due to its unique proton-sponge effect. , The presence of amine groups in the polymer backbone enables its covalent coupling with several functionalities/biomolecules and the formation of 3D nanomatrices with a huge internal space and a soft skeleton structure. This results in an improved encapsulation efficiency of drug molecules, thanks to the electrostatic interactions with the LPEI positive charge density.…”