Novel Multifunctional Stimuli-Responsive Nanoparticles for Synergetic Chemo–Photothermal Therapy of Tumors

Abstract

In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo–photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly­(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA–DOX@PDA–FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA–DOX@PDA–FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo–photothermal therapy of tumors.

Folic Acid–Functionalized Metal-Organic Framework Nanoparticles as Drug Carriers Improved Bufalin Antitumor Activity Against Breast Cancer

“…Cy5 was encapsulated in the MOF and FA-MOF. MOF/Cy5 and FA-MOF/Cy5 (200 μL, Cy5 concentration: 2.5 × 10 −5 mol/L) were injected through the tail vein of 4T1 (folate receptor was overexpressed) ( Chen et al, 2017 ; Pu et al, 2019 ) tumor–bearing xenografted mice. Fluorescence imaging of the tumor-bearing mice was performed at 0, 0.5, 4, 8, 24, and 48 h post injection using a small animal in vivo fluorescence imaging system (LIVIS Lumina series III (PerkinElmer, Waltham, MA, United States).…”

“…Subcutaneous tumors were established in nude mice (BALB/c, female, 4–6 weeks old) by injecting 4T1 cells (folate receptor was overexpressed) ( Chen et al, 2017 ; Pu et al, 2019 ) (2×10 6 cells in 0.2 ml PBS) into the left shoulder of the nude mice. Once the tumor volumes reached 100 mm 3 , the mice were randomized into five groups with six mice per group: normal saline group, MOF group, Buf solution group (2 mg/kg Buf), MOF/Buf group (2 mg/kg Buf), and FA-MOF/Buf group (2 mg/kg Buf).…”

The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives

“…The microenvironment in which a tumor is located has many different characteristics than that in normal physiological tissue [95]. Tumor microenvironment-based pH-based nanoparticles are one of the most studied stimulus-responsive drug nanocarriers and are sensitive to acidic environments inside and outside tumor cells [96][97][98]. Some modified COSs as carriers have been widely studied, operating according to the changes in the microenvironment to form a pH-specific response to release antitumor drugs.…”

Design and Applications of Tumor Microenvironment-Responsive Nanogels as Drug Carriers

“…Currently, nanogels with carboxyl or/and amino groups in the molecular structure are commonly used as pH-responsive drug delivery vehicles. The pH and thermo sensitive nanogels with DOX loading composed of poly (N-isopropylacrylamide-coacrylicacid) core, a polydopamine layer and an outer folic acid layer were designed and developed (Pu et al, 2021). With the decrease of pH from 7.4 to 5.5, the cumulative DOX release amount improved from 17.6 to 56.5%.…”