pH/Thermal Dual-Sensitive Nanoparticle-Hydrogel Composite Based on Pluronic and Carboxymethyl Chitosan for In Situ Injection and Enhanced Chemo-Photothermal Antitumor Effect

Abstract

The purpose of this paper is to develop a pH/thermal sensitive nanohydrogel composite for in situ injection and to achieve an enhanced chemo-photothermal synergistic antitumor effect. Pluronic F127 was oxidized to aldehyde-terminated (AF127) as the precursor of the thermally sensitive hydrogel. A series of hydrogels (HG) with different rheological behaviors were obtained by adjusting the ratio of AF127 to carboxymethyl chitosan (CMCS) (AF45/CM15, AF75/CM15, and AF90/CM15). By changing the ratio of AF127 micelles to CMCS, we can adjust the sol–gel transition time and temperature to facilitate in situ tumor injection. Indocyanine green (ICG) encapsulated AF127 micelles and doxorubicin (DOX)-loaded CMCS nanoparticles (NP-DOX) can form nanohydrogel composite (HG/ICG/NP-DOX) through dynamic Schiff base covalent bonds and physical entanglement. The nanohydrogel composite has good fluidity for injection at low temperatures and can quickly form hydrogel at 37 °C. Bromelain was introduced into the complex to improve the penetration of nanoparticles by hydrolyzing the dense extracellular matrix (ECM) in tumor tissue. ICG can produce a photothermal effect under 808 nm laser irradiation, further enhancing the antitumor effect of NP-DOX. HG/ICG/NP-DOX can remain in the tumor area for a long time, and it still shows an obvious photothermal effect even after 120 h. HG/ICG/NP-DOX with laser irradiation possesses an excellent chemo-photothermal synergistic antitumor effect, and the tumor growth inhibition rate reached 93.9%. These nanohydrogel composites have great potential in the field of in situ tumor injection as local drug delivery systems.

Injectable Thermogelling Nanostructured Ink as Simultaneous Optical and Magnetic Resonance Imaging Contrast Agent for Image-Guided Surgery

“…The optical ranges for both absorption and emission of the ICG dye are in the so-called first biological window (BW1, 700–950 nm range), optimal for in vivo applications, since in this range the biological tissues show low autofluorescence and they are much more transparent to the radiation concerning the UV and visible spectral regions. For this reason, ICG is one of the most used optical contrast agents for the IGS practice, being also approved by the Food and Drug Administration (USA), , and employed in clinical practice . A critical limitation of the use of such a molecule regards its very short retention time within the place of injection due to its speedy diffusion toward the surrounding biological tissues, which is strongly unfavorable for clinical applications whenever a precise marking of a tissue portion is needed.…”

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal–Photodynamic Anti-Tumor Therapy

“…Malignant tumors have continued to be one of the major threats to human health, closely related with a high mortality and recurrence rate [1]. In order to cure the cancer cells, doxorubicin (DOX) has been prominently used for various types of liver, breast [2], and colon tumors [3].…”