ABSTRACT
Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.
Subject(s)
Adenosine Triphosphate , Antineoplastic Agents , Infrared Rays , Animals , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/chemistry , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Immunotherapy , Drug Repositioning , Humans , Lasers , Photothermal Therapy , Mice, Inbred BALB C , Cell Proliferation/drug effects , Cell Line, Tumor , Alginates/chemistry , Female , Hydrogels/chemistry , Hydrogels/pharmacology , Drug Screening Assays, Antitumor , Particle Size , Artemisinins/chemistry , Artemisinins/pharmacologyABSTRACT
Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.
Subject(s)
Hyperthermia, Induced , Neoplasms , Humans , Polymers , Photothermal Therapy , Phototherapy , Neoplasms/drug therapy , Tumor MicroenvironmentABSTRACT
There is increasing popularity in the use of herbal medicine for different ailments as these natural products are considered safer than conventional medicines; however, their use in dosage exceeding prescribed limits can result in serious toxic side effects. We present a case of a 63-year old male who presented with complaints of restlessness, nausea, vomiting and tingling sensation on his body and ECG evidence of bi-directional ventricular tachycardia. On interrogation, it was revealed that the patient had self-prepared and consumed large quantity of an herbal medication (containing toxic aconite roots) as therapy for erectile dysfunction resulting in a fatal outcome.