Constructing a drug release model by central composite design to investigate the interaction between drugs and temperature-sensitive controlled release nanoparticles.

To study the release behavior of a thermosensitive controlled release drug delivery system and construct a predictable mathematical model of drug release, poly(N-isopropylacrylamide-co-Allylamine) (P(NIPA-AL17)) and ploy(styrene sulfonate) (PSS) were functionalized on the surface of hollow mesoporous carbon nanoparticles (HMCNs) through layer-by-layer (LBL) assembly to construct a photothermal responsive controlled release system. A five-level four-factorial central composite design (CCD) was performed to investigate the relationship between four independent variables including drug loading (A), number of polymer layers (B), temperature (C) and vibration rate of the shaker (D), and three dependent response variables, including cumulative release over 1 h (Y1), cumulative release over 24 h (Y2) and the release rate constant k (Y3). The CCD results indicate that A and C significantly affect Y1 (P < 0.05). C significantly affects Y2 (P < 0.05). A and B is found to affect Y3 (P < 0.05) significantly. When C is below 39 °C, Y1 and Y2 decrease with the increase of A and B, and when C is above 39 °C, they increase with the increase of A and B; Y3 decreases as A and B increase; and D shows the least or even no influence on Y1, Y2 and Y3. The constructed predictable mathematical model will provide a scientific reference for the further development and application of photothermal responsive controlled-release preparations.

Triple stimuli-responsive ZnO quantum dots-conjugated hollow mesoporous carbon nanoplatform for NIR-induced dual model antitumor therapy.

Aiming at the inefficiency and toxicity in traditional antitumor therapy, a novel multifunctional nanoplatform was constructed based on hollow mesoporous carbon (HMC) to achieve triple stimuli response and dual model antitumor therapy via chemo-photothermal synergistic effect. HMC was used as an ideal nanovehicle with a high drug loading efficiency as well as a near-infrared (NIR) photothermal conversion agent for photothermal therapy. Acid-dissoluble, luminescent ZnO quantum dots (QDs) were used as the proper sealing agents for the mesopores of HMC, conjugated to HMC via disulfide linkage to prevent drug (doxorubicin, abbreviated as Dox) premature release from Dox/HMC-SS-ZnO. After cellular endocytosis, the Dox was released in a pH, GSH and NIR laser triple stimuli-responsive manner to realize accurate drug delivery. Moreover, the local hyperthermia effect induced by NIR irradiation could promote the drug release, enhance cell sensitivity to chemotherapeutic agents, and also directly kill cancer cells. As expected, Dox/HMC-SS-ZnO exhibited a high drug loading capacity of 43%, well response to triple stimuli and excellent photothermal conversion efficiency η of 29.7%. The therapeutic efficacy in 4T1 cells and multicellular tumor spheroids (MCTSs) demonstrated that Dox/HMC-SS-ZnO + NIR had satisfactory chemo-photothermal synergistic effect with a combination index (CI) of 0.532. The cell apoptosis rate of the combined treatment group was more than 95%. The biodistribution and pharmacodynamics studies showed its biosecurity to normal tissues and synergistic inhibition effect to tumor cells. These distinguished results indicated that the Dox/HMC-SS-ZnO nanoplatform is potential to realize efficient triple stimuli-responsive drug delivery and dual model chemo-photothermal synergistic antitumor therapy.

Graphene quantum dots-gated hollow mesoporous carbon nanoplatform for targeting drug delivery and synergistic chemo-photothermal therapy.

BACKGROUND: Carbon-based drug delivery systems have attracted great interest because of their excellent photothermal conversion capability and high specific surface area for drug loading. Herein, we report a multifunctional nanoplatform based on hyaluronic acid (HA)-modified and graphene quantum dot (GQD)-gated hollow mesoporous carbon nanoparticle (HMCN) for anticancer drug encapsulation and targeted chemo-photothermal therapy of CD44 receptor-overexpressed cancer cells. METHODS: In this design, HMCN was not only used as a nanocarrier with high drug loading content to achieve chemotherapy, but also as a near-infrared absorbing agent to realize photothermal therapy. GQDs could not only prevent premature drug release during blood circulation, but also enhance the chemo-photothermal therapeutic efficacy for complete tumor growth suppression. After being modified with HA, the HA-HMCN(DOX)@GQDs could specifically target cancer cells. RESULTS: As expected, the as-prepared HMCN exhibited high doxorubicin (DOX)-loading capacity of 410 mg/g and excellent light-to-heat conversion property. The DOX was released from HA-HMCN(DOX)@GQDs in a near-infrared laser and pH stimuli-responsive manner, which could enhance the therapeutic effect. In vitro cell biological experimental results confirmed that the nanoplatform possesses excellent biocompatibility, specifically target CD44 receptor-overexpressing human cervical carcinoma HeLa cells, and has remarkable synergistic chemo-photothermal killing capacity. The in vivo therapeutic studies in HeLa xenografts also showed negligible toxicity of HA-HMCN@GQDs and complete inhibition of tumor growth of HA-HMCN(DOX) @GQDs with near-infrared irradiation. CONCLUSION: The excellent therapeutic effects demonstrated in vitro and in vivo suggested the HMCN-based nanoplatform holds potential for efficient dual-responsive targeting drug delivery and synergistic chemo-photothermal therapy.