A pH-response chemotherapy synergistic photothermal therapy for tumor suppression and bone regeneration by mussel-inspired Mg implant

Abstract

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor in vitro and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.

Electro-Responsive Conductive Blended Hydrogel Patch

“…In general, negatively charged drugs are released by a reduction of the drug carrier, whereas positively charged drugs are released by oxidation [ 57 , 58 ]. The DOX used in this experiment was a positively charged drug [ 59 ]. When the ES application was generated, the movement of free counter ions in the electric field could create a high osmotic pressure inside the hydrogel structure to release the DOX [ 60 ].…”

Recent advances in regenerative biomaterials

“…For example, self-assembly of amphiphilic polymers can be employed to significantly improve the bioavailability of hydrophobic drugs [ 336 , 337 ]; appropriate nanotechnology can lower the adverse effect owing to the accumulation of drug in tumor tissue via passive target etc. [ 338–340 ]; prodrug micelles are capable of protecting API via covalently bonding an API to amphiphilic polymers [ 341 , 342 ]; PEGylation, namely, covalently grafting a PEG polymer to a drug can enhance the therapeutic properties of API by prolongation of the drug circulation in plasma [ 343 ]; even simply mixing with PEG can enhance the fraction of the active chemical form of antitumor drugs of the camptothecin family by modification of drug–material interaction [ 344 ]; cell-derived biomimetic nanoparticles endow drugs with many features such as active target, low immunogenicity and long circulation time [ 345–348 ]; various responsive polymers have been tried to positively affect the controlled release of API [ 349–351 ]; scaffolds loaded with drugs or modified with other biologically active moieties have been employed to support tissue regeneration [ 352–354 ]. All of these indicate that the modern drug delivery system (DDS) is based on the development of exciting materials to a large extent and the development of an advanced DDS is in turn beneficial for regenerative medicine.…”

Mussel-Inspired Polydopamine-Based Multilayered Coatings for Enhanced Bone Formation

“…Due to the similar structure to melanin, PDA exhibits photothermal property, whose conversion efficiency under near-infrared (NIR) is about 40%. Notably, NIR-induced photothermal therapy is considered a promising strategy for tumor treatment without damaging surrounding tissues ( Ma et al, 2016 ; Shao et al, 2021 ). Meanwhile, due to the functional groups of PDA, antitumor drugs can be loaded in multilayered coatings, which can be released in a sustained manner.…”

“…The application of antitumor and anti-tuberculosis drugs to assist osteogenesis also have been explored in specific situations. Shao et al ( Shao et al, 2021 ) loaded doxorubicin on Mg alloy via PDA intermediate coating for bone reconstruction after resection of primary malignant bone tumors. The multilayered coating showed outstanding photothermal property and sustained doxorubicin release for tumor inhibition, where the osteogenic activity was also enhanced.…”

“…After resection of bone tumors, the resultant bone defects will largely influence patients’ life quality. It is beneficial to carry out bone reconstructions via tissue engineering, but the tumor cells are hard to remove completely and the local relapse can occur due to residual tumor cells, which will have negative effects on bone regeneration and even lead to failure due to the poor bone reconstruction for tumor-related bone defects ( Shao et al, 2021 ). Therefore, in order to repair bone defects after tumor section, the scaffolds should exhibit antitumor and osteogenic property.…”