Hyaluronic Acid Nanomicelles for Photo-chemodynamic Antitumor Therapy

Abstract

Cancer cell immune escape, metastasis, invasion, and recurrence are closely related to high immune-checkpoint expression and tumor hypoxia. Immune-checkpoint inhibition and tumor hypoxia regulation have therefore garnered attention in cancer therapeutics. This study found that the methyl pyropheophorbide-a (MPPa) derivative complex 31,32,7,8-tetrahydroxy-4H-MPPa-Cu2+ (HMPPa-Cu) induces apoptosis in tumor cells to activate immunogenicity. HMPPa-Cu combined with anti-programmed death ligand 1 (PD-L1) immune-checkpoint blockade (ICB) therapy not only eradicates light-irradiated primary CT26 colon cancer but also inhibits untreated distant tumors. HMPPa-Cu catalyzes hydrogen peroxide decomposition to generate oxygen in situ and increase the cellular oxygen concentration. To enable HMPPa-Cu tumor targeting and increase its cell uptake capacity, HMPPa-Cu was embedded with hyaluronic acid–cinnamaldehyde nanomicelles (NMs) to obtain HCHC NMs. Acid stimulation of the HCHC NMs released free HMPPa and Cu2+ and significantly increased the quantum yield of singlet oxygen. The tumor microenvironment and near infrared stimulation activated chemodynamic therapy (CDT) and photodynamic therapy (PDT) synergistically. Cu2+ depleted glutathione (DG) to amplify the reactive oxygen species and simultaneously underwent in situ oxygenation (ISO). HCHC NMs-mediated PDT/CDT/ISO/DG significantly improved the therapeutic effect of ICB.

Serum sirtuin1: a potential blood biomarker for early diagnosis of Alzheimer’s disease

“…The most accurate way to diagnose Alzheimer’s disease is to perform brain dissection on the patient’s brain tissue and determine whether the subject has typical pathological manifestations of Alzheimer’s disease, such as neuroinflammatory plaques and neurofibrillary tangles, to determine whether the subject has Alzheimer’s disease [ 8 , 9 ]. However, due to the non-feasibility of such methods, to diagnose and conclude the conditions, medical practitioners mainly depend on clinical symptoms, physical examination, MMSE, positron emission tomography (PET) of tracer molecules [ 10 ] and analysis of cerebrospinal fluid (CSF) proteins [ 11 ] and use tests to examine a patient’s mental ability [ 9 , 12 , 13 ]. However, the sensitivity and specificity of such tests are usually not high enough; thus, these tests cannot be used to make an effective and accurate judgment of the disease.…”