TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles(NPs)have shown potential in cancer therapy,while a single administration conferring a satisfactory outcome is still unavailable.To address this issue,the dissolving microneedles(DMNs)were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy(PTT).α-Tocopheryl polyethylene glycol succinate(TPGS)/hyaluronic acid(HA)dualfunctionalized PLGA NPs(HD10 NPs)were fabricated to co-load paclitaxel and indocyanine green.HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS,respectively.PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period,highly activating caspase 3 enzyme,and significantly reducing the expression of survivin and MMP-9 proteins.Further,the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4 T1 tumorbearing mice.After a single administration,HD10 NPs delivered with DMNs showed the best antitumor effect when giving chemotherapy alone.As expected,the anti-tumor effect was profoundly enhanced after combined therapy,and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection.Moreover,DMNs showed better safety due to moderate hyperthermia.Therefore,the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

Endoscopic mucosal resection vs endoscopic submucosal dissection for superficial non-ampullary duodenal tumors

BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors(SNADETs)is controversial.AIM To compare the efficacy and safety of endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)for SNADETs.METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs,which included eight hospitals in Fukuoka,Japan,between April 2001 and October 2017.A total of 142 patients with SNADETs treated with EMR or ESD were analyzed.Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups.We analyzed the treatment outcomes,including the rates of en bloc/complete resection,procedure time,adverse event rate,hospital stay,and local or metastatic recurrence.RESULTS Twenty-eight pairs of patients were created.The characteristics of patients between the two groups were similar after matching.The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group[median procedure time(interquartile range):6(3-10.75)min vs 87.5(68.5-136.5)min,P<0.001,hospital stay:8(6-10.75)d vs 11(8.25-14.75)d,P=0.006].Other outcomes were not significantly different between the two groups(en bloc resection rate:82.1%vs 92.9%,P=0.42;complete resection rate:71.4%vs 89.3%,P=0.18;and adverse event rate:3.6%vs 17.9%,P=0.19,local recurrence rate:3.6%vs 0%,P=1;metastatic recurrence rate:0%in both).Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation.CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD,and provides acceptable curability and safety compared to ESD.Accordingly,EMR for SNADETs is associated with lower medical costs.

Clinical outcomes of endoscopic resection of superficial nonampullary duodenal epithelial tumors: A 10-year retrospective, single-center study

BACKGROUND Although premalignant duodenal lesions such as adenomas are uncommon,the incidences of these lesions have increased in recent times,and thus,the demand for minimally invasive treatments such as endoscopic resection(ER)has also increased.However,ER in the duodenum is more challenging than ER in other locations of the gastrointestinal tract.AIM To evaluate the safety and efficacy of ER for superficial nonampullary duodenal epithelial tumors(SNADETs)METHODS We performed a retrospective observational study on 56 consecutive patients(58 lesions)diagnosed with SNADETs that underwent ER from January 2011 to December 2020 at Yeungnam University Hospital.Patient demographics,lesion characteristics,and procedural and technical data were collected,and clinical outcomes,including procedure-related complications,completeness of resection,and recurrence were analyzed.RESULTS Median patient age was 57 years[range,26–77,30(53.6%)men].Endoscopic mucosal resection(EMR)was performed on 57 lesions(98.3%)and snare polypectomy on one(1.7%).Lesions consisted of 52 adenomas with low-grade dysplasia(89.7%),3 adenomas with high-grade dysplasia(5.2%),and 3 intramucosal adenocarcinomas(5.2%).There were 16 cases of intraprocedural bleeding(27.6%)and 1 case of delayed bleeding(1.7%),and all these 17 cases were successfully managed endoscopically.No perforation or procedure-related death occurred.Larger lesion size was associated with an increased risk of EMR-related bleeding(P=0.033).During a median follow-up period of 23 mo(range 6–100 mo),no local recurrence occurred,despite the fact one-third of the patients(19 lesions,32.8%)underwent piecemeal resection and 3 patients(3 lesions,5.2%)that underwent en bloc resection had a pathologically determined positive lateral margin.No patient died from a primary duodenal neoplasm.CONCLUSION The majority of SNADETs can be safely and curatively resected by EMR,and thus,based on consideration of the high incidence of fatal complications attributable to ESD,we conclude EMR,including piecemeal resection,should be considered the treatment of first choice for SNADETs.

Self-assembly nanomicelle-microneedle patches with enhanced tumor penetration for superior chemo-photothermal therapy

Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.