T1-Positive Mn2+-Doped Multi-Stimuli Responsive poly(L-DOPA) Nanoparticles for Photothermal and Photodynamic Combination Cancer Therapy

Abstract

In this study, we designed near-infrared (NIR)-responsive Mn2+-doped melanin-like poly(L-DOPA) nanoparticles (MNPs), which act as multifunctional nano-platforms for cancer therapy. MNPs, exhibited favorable π-π stacking, drug loading, dual stimuli (NIR and glutathione) responsive drug release, photothermal and photodynamic therapeutic activities, and T1-positive contrast for magnetic resonance imaging (MRI). First, MNPs were fabricated via KMnO4 oxidation, where the embedded Mn2+ acted as a T1-weighted contrast agent. MNPs were then modified using a photosensitizer, Pheophorbide A, via a reducible disulfide linker for glutathione-responsive intracellular release, and then loaded with doxorubicin through π-π stacking and hydrogen bonding. The therapeutic potential of MNPs was further explored via targeted design. MNPs were conjugated with folic acid (FA) and loaded with SN38, thereby demonstrating their ability to bind to different anti-cancer drugs and their potential as a versatile platform, integrating targeted cancer therapy and MRI-guided photothermal and chemotherapeutic therapy. The multimodal therapeutic functions of MNPs were investigated in terms of T1-MR contrast phantom study, photothermal and photodynamic activity, stimuli-responsive drug release, enhanced cellular uptake, and in vivo tumor ablation studies.

Highly Conductive Melanin-like Polymer Composites for Nonenzymatic Glucose Biosensors with a Wide Detection Range

“…Chemical Synthesis of PLDA NPs. PLDA NPs were synthesized through KMnO 4 oxidation of L-DOPA according to the previous method published by Kang et al 38 Briefly, L-DOPA (200 mg) was dissolved in 190 mL of deionized water under vigorous stirring. Then, 10 mL of a KMnO 4 solution (10 mM) was added to the L-DOPA aqueous solution and stirred at 50 °C for 12 h. The mixed solution was centrifuged with Amicon Ultra Centrifugal Filters (EMD Millipore, Darmstadt, Germany) at 4000 rpm for 10 min and washed three times with deionized water.…”

Polydopamine/IR820 nanoparticles as topical phototheranostics for inhibiting psoriasiform lesions through dual photothermal and photodynamic treatments

“…10,28 It is also possible that the NIR-generated hyperthermia synergistically elevated the endocytosis of the photothermal nanoparticles. 29 Therapy based on the regulation and inhibition of keratinocyte proliferation is practical to treat psoriasis. After entering the keratinocytes, both PDA and IR820 could exhibit the photothermal effect triggered by NIR leading to cell damage.…”

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…In addition, Kang etal. ( 64 ) prepared dual laser-responsive multifunctional melanin-like nanoparticles (MNPs) for PDT, PTT, and chemotherapy, based on the KMnO4-oxidative polymerization of L-3,4-dihydroxyphenylalanine (L-DOPA), pheophorbide a, and Dox, and modified by FA. The results of antitumor experiments showed that after 670-nm and 808-nm laser irradiation, the MNP group showed more extensive damage and apoptosis than the control group, showing great potential for antitumor therapy.…”