Research progress of ectopic thyroid cancer in thyroglossal duct cyst: A case report and literature review.

RATIONALE: Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease. PATIENT CONCERNS: A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities. DIAGNOSES: Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma. INTERVENTIONS: A Sistrunk operation and ipsilateral thyroidectomy were performed. OUTCOMES: Postoperative recovery was satisfactory. LESSONS: Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.

Renal pelvis sarcomatoid carcinoma with renal vein tumor thrombus: A case report and literature review.

BACKGROUND: Renal pelvis sarcomatoid carcinoma (RPSC) is a rare and aggressive malignancy whose diagnosis is difficult because radiological imaging results can lead to misclassification as a more common type of renal tumor. In addition, clinical management of patients with RPSC is difficult because of the limited efficacy of available treatments. In this study, we present a comprehensive description of a patient who presented with RPSC and a simultaneous renal vein tumor thrombus. CASE SUMMARY: During April, 2020, a 64-year-old female presented with an isolated episode of hematuria accompanied by abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a lesion in the right renal pelvis. We therefore performed a radical nephrectomy of the right kidney. The subsequent histopathological and immunological results verified the diagnosis of RPSC. Despite administration of 6 cycles of a gemcitabine-cisplatin regimen, the patient's condition progressively deteriorated, and she died about 15 mo after the nephrectomy. CONCLUSION: We performed a comprehensive analysis of a patient with RPSC that included CT, MRI, immunohistochemistry, and genetic testing. The insights from our detailed analysis of this patient and our concomitant review of the literature may assist clinicians in their diagnosis and treatment of RPSC.

Differences of Escherichia coli isolated from different organs of the individual sheep: molecular typing, antibiotics resistance, and biofilm formation.

Despite numerous studies on Escherichia coli (E. coli) from sheep, there have been few reports on the characterization of E. coli isolates from various organs of individual sheep until now. The present study conducted molecular typing, antibiotics resistance, biofilm formation, and virulence genes on E. coli isolated from 57 freshly slaughtered apparently healthy sheep carcasses, gallbladders, fecal samples, and mesenteric lymph nodes (MLNs). The results demonstrated that the detection rate of R1 LPS core type in E. coli isolated from fecal samples (70.83%) was higher than that from other organs, but the detection rate of antibiotic resistance genes was lower (P < 0.05). The predominant phylogenetic group of E. coli isolated from the carcasses was group B1 (93.33%), and the detection rate of multidrug-resistance phenotype (80%) and the resistance rate of E. coli was higher than that from other organs (P < 0.05). Interestingly, the intensity of biofilm formation of E. coli isolated from MLNs was higher than that from other organs (P < 0.05). However, except for ibeB, the detection rates of virulence genes did not differ in E.coli isolated from different organs. In conclusion, differences were noted in these parameters of E. coli isolated from different organs of individual sheep. Therefore, the data may contain considerable mistakes concerning the actual situation in the host if we only analyze the data of E. coli isolated from feces or carcasses.

Comparation of intraureteral stent and conventional stent at different stages: a systematic review with meta-analysis.

INTRODUCTION: Stent related symptom (SRS) is the most common adverse effect of ureteral stenting. In recent years, many efforts have been made to develope modified ureteral stents to ameliorate SRS. It has been reported that intraureteral stents have the potential to improve the tail end adverse effect of the bladder and alleviate SRS. However, there still lack of evidence for the efficacy and the safety of clinically applying intraureteral stents. The aim of this work is to investigate the efficacy and safety of intraureteral stents. EVIDENCE ACQUISITION: A systematic review was performed by using the PubMed, Web of Science, Medline, Embase, and Cochrane library. The studies published before February 2023 were included. The study selection was following the guideline from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The searching strategy was: "Pigtail suture stent" OR "Intra-ureteric stent" OR "Suture Stent" OR "Intraureteral stent" AND "Ureteroscopy" OR "Urinary calculi" OR "Stent-related symptoms" OR "Lower urinary tract symptoms". The data from randomized clinical trials which meet the selection criteria were extracted. Revman 5.4 was employed to proceed the meta-analysis. EVIDENCE SYNTHESIS: A total of six randomized clinical trials of intraureteral stents were included in this systematic review and meta-analysis. According to the different investigation time, the results could be divided into four stages: early-stage, middle-stage, late-stage, and long-term evaluation. Urinary symptoms, pain score, and general health were significantly improved in intraureteral stents group at middle stage. For late-stage, intraureteral stent achieved better outcomes in urinary symptoms index, VAS score, quality of life, general health, and pain score. However, for early-stage and long-term evaluation, there was no significant difference between two groups. CONCLUSIONS: This systematic review and meta-analysis reveal that regardless of the stage of treatment, the efficacy and safety of intraureteral stent are no worse than that of conventional stent. During 7-14 days postoperation, which is the most commonly time for clinically using ureteral stent, most of the outcomes of intraureteral stent are better than those of conventional stent. Hence, it is confirmed that intraureteral stent is worth for more clinical study and application.

Combination therapy for high-volume versus low-volume metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.

Purpose: To conduct a systematic review and network meta-analysis (NMA) to compare the efficacy of currently available combination therapies in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: Qualified publications were searched in the PubMed, Embase, and Cochrane CENTRAL databases. Overall survival (OS) and radiographic progression-free survival (rPFS) were indirectly compared and assessed using NMA and the surface under the cumulative ranking curve, respectively. Adverse events (AEs) were also compared. Results: Eighteen publications from 12 trials were analyzed in the NMA. In the overall population, triplet therapy was ranked first for OS (hazard ratio [HR]: 0.57, 95% credible interval [CrI]: 0.48-0.67) and rPFS (HR: 0.33, 95% CrI:0.26-0.41) compared with androgen deprivation therapy (ADT) with or without standard non-steroidal antiandrogen. In high-volume mHSPC, triplet therapy was also ranked first in OS (HR, 0.57; 95% CrI:0.44-0.75) and rPFS(HR, 0.29; 95% CrI: 0.23-0.37). Specifically, abiraterone triplet therapy was ranked first in OS (HR, 0.52; 95% CrI:0.38-0.72) and rPFS (HR, 0.28; 95% CrI:0.21-0.38) among all therapies. ADT plus rezvilutamide was ranked first among doublet therapies (OS: HR, 0.58; 95% CrI:0.44-0.77; rPFS: HR, 0.44; 95% CrI:0.33-0.58). In low-volume mHSPC, doublet and triplet therapies were ranked first in OS (HR:0.68, 95% CrI:0.58-0.80) and rPFS (HR:0.37, 95% CrI:0.25-0.55), respectively. ADT plus apalutamide was ranked first in OS among all therapies (HR:0.53, 95% CrI:0.35-0.79), whereas enzalutamide triplet therapy was ranked first in rPFS (HR:0.27, 95% CrI:0.15-0.51). ADT plus rezvilutamide showed a relatively lower incidence of AE among all therapies (OR:1.00, 95% CrI:0.31-3.15), and a lower risk of specific AEs among doublet therapies, particularly regarding seizure (OR, 0.29; 95% CrI:0.01-8.18) and fatigue (OR, 0.96; 95% CrI:0.63-1.46). Docetaxel-based doublet or triplet therapies significantly increased the risk of any AEs or grade ≥3 AEs. Conclusion: Triplet therapy was the best treatment option for the overall population. In high-volume mHSPC, triplet therapy and ADT plus rezvilutamide had the greatest potential to benefit patients. Patients with low-volume mHSPC were most likely to benefit from ADT plus androgen receptor-targeted agents. Triplet therapy was associated with a higher risk of AEs than the other therapies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375347, identifier PROSPERO:CRD42022375347.

In Situ-Generated CuI Catalytic System for Oxidative N-Formylation of N-Heterocycles and Acyclic Amines with Methanol.

The development of a sustainable and simple catalytic system for N-formylation of N-heterocycles with methanol by direct coupling remains a challenge, owing to many competing side reactions, given the sensitivity of N-heterocycles to many catalytic oxidation or dehydrogenation systems. This work concerns the development of an in situ-generated CuI catalytic system for oxidative N-formylation of N-heterocycles with methanol that is based on the case study of a more typical 1,2,3,4-tetrahydroquinoline as substrate. Aside from N-heterocycles, some acyclic amines are also transformed into the corresponding N-formamides in moderate yields. Furthermore, a probable reaction mechanism and reaction pathway are proposed and extension of work based on some findings leads to a demonstration that the formed ⋅O2 - and ⋅OOH radicals in the catalytic system is related to the formation of undesired tar-like products.

Solitary fibrous tumor of the renal pelvis: A case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm. SFT derived from the renal pelvis is an exceedingly rare entity. In this study, we report a case of renal pelvis SFT and review the relevant literature on this rare tumor. CASE SUMMARY: A 76-year-old man was hospitalized due to right lumbar and abdominal pain. Abdominal computed tomography showed a hypervascular space-occupying renal lesion, sized 2.3 cm × 1.8 cm. Based on the computed tomography findings, the patient was diagnosed with right renal pelvis tumor and underwent nephrectomy. Postoperative immunohistochemical results confirmed the diagnosis. As of the 3-year follow-up, there were no signs of recurrence, and the patient has recovered well. CONCLUSION: We report a rare case of SFT derived from the renal pelvis and discuss the imaging and histopathological features that distinguish renal pelvis SFT from other renal pelvis tumors.

Therapeutic effects of recombinant SPLUNC1 on Mycoplasma ovipneumoniae-infected Argali hybrid sheep.

Clinical therapeutic and immunoregulatory effects of recombinant SPLUNC1 protein (rSPLUNC1) were evaluated in Mycoplasma ovipneumoniae (Mo)-infected Argali hybrid sheep (AHS). Group A contained six Bashibai sheep (BS) and groups B-D contained six AHS each. All sheep were manually infected with Mo. Five days post-infection, rSPLUNC1 from BS and AHS was injected intratracheally into group C and D animals; physiological saline was administered to groups A and B. Serum IL-5, IL-6, and IL-9 were quantified by ELISA. After sacrificing the sheep, lung tissues were extracted for pathological examination. The qPCR was used to quantify Mo load in the lungs and evaluate therapeutic efficacy. Serum IL-5, IL-6, and IL-9 concentrations increased during early infection stages in all groups but were significantly lower in groups A, C, and D than in group B on days 14 and 21. On day 21, IL-5 concentrations were lower in group A than in groups C and D. IL-6 concentration in groups A, C, and D was significantly lower than that in group B, and that in groups C and D was significantly lower than that in group A. Mean mycoplasma pneumonia histopathology scores were significantly lower in groups C and D than in group B, and Mo load in group C and D lung tissue decreased significantly compared to that in group B. Intratracheal injection of rSPLUNC1 into Mo-infected sheep decreased the cytokine levels and alleviated clinical symptoms with no mortality. rSPLUNC1 had significant therapeutic effects on Mo-infected AHS and can regulate pro-inflammatory cytokines.

Comprehensive RNA-Seq profiling of the lung transcriptome of Bashbay sheep in response to experimental Mycoplasma ovipneumoniae infection.

The Bashbay sheep (Ovis aries), an indigenous breed of Xinjiang, China, has many excellent characteristics. It is resistant to Mycoplasma ovipneumoniae infection, the causative agent of mycoplasma ovipneumonia, a chronic respiratory disease that is harmful to the sheep industry. To date, knowledge regarding the mechanisms responsible for M. ovipneumoniae pathogenesis in scant. Herein, we report the results of transcriptome profiling of lung tissues from Bashbay sheep experimentally infected with an M. ovipneumoniae strain at 4 and 14 days post-infection, in comparison to mock-infected animals (0 d). Transcriptome profiling was performed by deep RNA sequencing, using the Illumina platform. The analysis of differentially expressed genes was performed to determine concomitant gene-specific temporal patterns of mRNA expression in the lungs after M. ovipneumoniae infection. We found 1048 differentially expressed genes (575 up-regulated, 473 down-regulated) when comparing transcriptomic data at 4 and 0 days post-infection, and 2823 (1362 up-regulated, 1461 down-regulated) when comparing 14 versus 0 days post-infection. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the differentially expressed genes at 4 and 14 versus 0 days post-infection were enriched in 245 and 287 pathways, respectively, and the Toll-like receptor (TLR) signaling pathway was considered most closely related to MO infection (p < 0.01). Two pathways (LAMP-TLR2/TLR6-MyD88-MKK6-AP1-IL1B and LAMP-TLR8MyD88-IRF5-RANTES) were identified based on the TLR signaling pathway from differentially expressed genes related M. ovipneumoniae infection. Gene Ontology analysis showed that differentially expressed genes in different groups were enriched for 1580 and 4561 terms, where those most closely related to M. ovipneumoniae infection are positive regulators of inflammatory responses (p < 0.01). These results could aid in understanding how M. ovipneumoniae infection progresses in the lungs and may provide useful information regarding key regulatory pathways.

Comprehensive RNA-Seq profiling of the lung transcriptome of Argali hybrid sheep in response to experimental Mycoplasma ovipneumoniae infection.

BACKGROUND: An experiment was conducted to reveal why the Argali hybrid sheep are susceptible to Mycoplasma ovipneumoniae infection, the causative agent of mycoplasma ovipneumonia, a chronic respiratory disease that is harmful to the sheep industry. RESULTS: After nine Argali hybrid sheep, divided into three groups, were experimentally infected with an M. ovipneumoniae strain at 0, 4 and 14 days, transcriptome profiling of lung tissues was performed by deep RNA sequencing, using the Illumina platform. Analysis of differentially expressed genes was performed to determine concomitant gene-specific temporal patterns of mRNA expression in the lungs after M. ovipneumoniae infection. 156 differentially expressed genes (44 up-regulated, 112 down-regulated) were found when comparing transcriptomic data at 4 and 0 days post-infection, and 367 (35 up-regulated, 332 down-regulated) when comparing 14 versus 0 days post-infection. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the differentially expressed genes at 4 and 14 versus 0 days post-infection were enriched in 109 and 150 pathways, respectively, and the Primary immunodeficiency pathway was considered most closely related to MO infection (p < .01). Hyper-IgM syndrome was identified based on the B-cell Immunodeficiency signaling pathway from differentially expressed genes related to M. ovipneumoniae infection. Gene Ontology analysis showed that differentially expressed genes in different groups were enriched for 497 and 928 terms, where those most closely related to M. ovipneumoniae infection are ciliated motor damage (p < .01). CONCLUSIONS: The situation that ciliary movement is significantly inhibited and B cells in immunodeficiency are possibly the most important reason why Argali hybrid sheep are susceptible to MO.

Advances in Drug Delivery via Biodegradable Ureteral Stent for the Treatment of Upper Tract Urothelial Carcinoma.

Drug eluting ureteral stent is an effective means for local drug delivery to the urinary tract. It can potentially solve a variety of upper urinary tract problems, such as stent-related urinary tract infections and discomfort, ureteral stricture, and neoplastic diseases. However, the release of drug elutes on the surface of biostable stents is unsustainable and uncontrollable. With the development of biomaterial science, the emergence of biodegradable ureteral stents (BUSs) provides a new approach for local drug delivery in the urinary tract. The drugs can be continuously released in a controlled manner from a drug-eluting BUS, when the stent degrades. Especially for the delivery of anti-tumor drugs, the stents can obviously improve the therapeutic effectiveness of the drugs by prolonging the contact duration of the drug and tumor cells. In addition, a secondary stent removal procedure can be avoided. The purpose of this review article is to provide an overview of anti-tumor drug-eluting BUSs and discuss the biomaterials and drug delivery systems of BUS that are currently being developed to deliver anti-tumor drugs for upper tract urothelial carcinoma.

Cell Membrane-Camouflaged Nanocarriers for Cancer Diagnostic and Therapeutic.

Cell membrane (CM)-camouflaged nanocarriers (CMNPs) are the tools of a biomimetic strategy that has attracted significant attention. With a wide range of nanoparticle cores and CMs available, various creative CMNP designs have been studied for cancer diagnosis and therapy. The various functional CM molecules available allow CMNPs to demonstrate excellent properties such as prolonged circulation time, immune escape ability, reduced systemic toxicity, and homologous targeting ability when camouflaged with CMs derived from various types of natural cells including red and white blood cells, platelets, stem cells, and cancer cells. In this review, we summarize various CMNPs employed for cancer chemotherapy, immunotherapy, phototherapy, and in vivo imaging. We also predict future challenges and opportunities for fundamental and clinical studies.

Laden Nanofiber Capsules for Local Malignancy Chemotherapy.

In contrast to systemic chemotherapy, the local administration of chemotherapeutics potentially optimizes their accumulation in the tumor tissues and alleviates the associated systemic toxicity. However, the lack of control over the release of encapsulated drugs and their degradation represents a major challenge for local drug delivery systems. In this study, we developed a series of epirubicin (EPI)-loaded poly(ε-caprolactone)/poly(lactide-co-glycolide) (PCL/PLGA) nanofiber capsules with adjustable rates of drug release and degradation for local malignancy chemotherapy. The core-sheath PCL/PLGA nanofiber capsules containing 15.0 or 25.0 wt% of PCL in the sheath and 0, 5.0, or 10.0 wt% of EPI in the core were produced by emulsion electrospinning technology. The EPI release and degradation of the nanofiber capsules could be accelerated by decreasing the PCL content in the sheath. More importantly, the EPI-loaded PCL/PLGA nanofiber capsules effectively inhibited the growth of tumor cells in vitro and in vivo. Moreover, none of the laden nanofiber capsules caused apparent systemic toxicity. Hence, the cytostatic-loaded electrospun polyester nanofiber capsules displayed controlled drug release and degradation, along with satisfactory antitumor properties, indicating their great potential in local malignancy chemotherapy.

Gradiently degraded electrospun polyester scaffolds with cytostatic for urothelial carcinoma therapy.

Kidney-sparing surgery is the preferred treatment strategy for low-risk upper tract urothelial carcinoma (UTUC). However, after this procedure, prevention of the carcinoma recurrence in the ureter and supporting the ureter with a ureteral stent are necessary. Biodegradable drug-loaded ureteral scaffolds are able to maintain their long-term effective drug concentrations in the lesion sites without the defects of traditional ureteral stents, which may address both issues simultaneously. The purpose of this study was to reveal the possibility of the controlled delivery of epirubicin (EPI) via gradiently degraded electrospun poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffolds to evaluate their antitumor activity against UTUC. The degradable PCL/PLGA scaffolds containing 15.0 and 25.0 wt% PCL and loading of 0, 5.0, and 10.0 wt% EPI were successfully fabricated via electrospinning. In addition, the PCL/PLGA scaffolds showed sustained and controlled degradation and drug release kinetics, that is, their degradation and drug release rates slowed with an increase in the ratio of PCL. The EPI-loaded PCL/PLGA scaffolds showed excellent antitumor activities both in vitro and in vivo without apparent systemic toxicity. Overall, the gradiently-degraded EPI-loaded electrospun polyester scaffolds are potential ureteral stent tubes for the local inhibition of the recurrence of UTUC, where the continued release of EPI can prevent the subsequent proliferation of residual tumor cells, and the gradient degradation is consistent with the repair of the ureter.

Polylactide-Cholesterol Stereocomplex Micelle Encapsulating Chemotherapeutic Agent for Improved Antitumor Efficacy and Safety.

For efficient therapy, optimized polymer micelle drug delivery systems require stability during circulation, appropriate diameters for targeting, and controlled drug release at the lesion site. To enhance the stability, adjust the sizes, and improve the selectivity of drug release of micelles from polylactides and polypeptides, stereocomplex interaction has been introduced. Herein, the cholesterol (CHOL)-enhanced doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (CDM/DOX), poly(L-lactide)-based micelle (CLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric 4-armed poly(ethylene glycol)-polylactide copolymers were reported to enhance tumor cell uptake and control drug release for treatment of cervical carcinoma. The introduction of hydrophobic CHOL further upregulated the stability, drug-loading capability, and cell uptake of micelles. All these DOX-loaded micelles showed appropriate sizes of ∼100 nm for the enhanced permeability and retention (EPR) effect. Compared to CDM/DOX and CLM/DOX, SCM/DOX exhibited the highest cell uptake and the most efficient antitumor efficacy in vitro. For U14 cervical carcinoma mouse model, all of the DOX-loaded micelles, especially SCM/DOX, effectively inhibited the progression of cervical carcinoma, as demonstrated by nearly stagnant tumor growth and increased apoptosis and necrosis areas within tumor tissue. Furthermore, these DOX-loaded micelles effectively alleviated the systemic toxicity of DOX. All the above results suggest that the DOX-loaded micelles, especially SCM/DOX, are an ideal drug delivery system for combating cervical carcinoma.

Emphysematous pyelonephritis and cystitis: A case report and literature review.

This present case report describes a 64-year-old female patient with type 2 diabetes mellitus who also had emphysematous pyelonephritis (EPN) and emphysematous cystitis (EC). Computed tomography revealed well defined emphysematous pyelonephritis and cystitis. Broad-spectrum antibiotic and percutaneous drainage of the right kidney were used as part of a conservative management regimen. The patient achieved clinical recovery and was discharged 12 days after admission. Furthermore, 13 other cases of EPC and EC that were reported between 1962 and 2017 were reviewed and discussed. The overall mortality was 15.4% (two of 13 patients), compared with 25% for EPN alone or 7.4% for EC alone as reported in the literature. The primary pathogen identified in the 13 patients was Escherichia coli (53.8%). All 13 patients were treated with antibiotics.

Poly(Ethylene Glycol)-Polylactide Micelles for Cancer Therapy.

For the treatment of malignancy, many therapeutic agents, including small molecules, photosensitizers, immunomodulators, proteins and genes, and so forth, have been loaded into nanocarriers for controllable cancer therapy. Among these nanocarriers, polymeric micelles have been considered as one of the most promising nanocarriers, some of which have already been applied in different stages of clinical trials. The successful advantages of polymeric micelles from bench to bedside are due to their special core/shell structures, which can carry specific drugs in certain disease conditions. Particularly, poly(ethylene glycol)-polylactide (PEG-PLA) micelles have been considered as one of the most promising platforms for drug delivery. The PEG shell effectively prevents the adsorption of proteins and phagocytes, thereby evidently extending the blood circulation period. Meanwhile, the hydrophobic PLA core can effectively encapsulate many therapeutic agents. This review summarizes recent advances in PEG-PLA micelles for the treatment of malignancy. In addition, future perspectives for the development of PEG-PLA micelles as drug delivery systems are also presented.

l-Cystine-Crosslinked Polypeptide Nanogel as a Reduction-Responsive Excipient for Prostate Cancer Chemotherapy.

Smart polymer nanogel-assisted drug delivery systems have attracted more and more attention in cancer chemotherapy because of their well-defined morphologies and pleiotropic functions in recent years. In this work, an l-cystine-crosslinked reduction-responsive polypeptide nanogel of methoxy poly(ethylene glycol)-poly(l-phenylalanine-co-l-cystine) (mPEG-P(LP-co-LC)) was employed as a smart excipient for RM-1 prostate cancer (PCa) chemotherapy. Doxorubicin (DOX), as a regular chemotherapy drug, was embedded in the nanogel. The loading nanogel marked as NG/DOX was shown to exhibit glutathione (GSH)-induced swelling and GSH-accelerated DOX release. Subsequently, NG/DOX showed efficient cellular uptake and proliferation inhibition. Furthermore, NG/DOX presented enhanced antitumor efficacy and security in an RM-1 PCa-grafted mouse model in vivo, indicating its great potential for clinical treatment.

Selective intracellular drug delivery from pH-responsive polyion complex micelle for enhanced malignancy suppression in vivo.

The pH-triggered intracellular drug delivery platforms have attracted great interest in malignancy therapy. Herein, a pH-responsive polyion complex (PIC) micelle from anionic acid-sensitive methoxy poly(ethylene glycol)-block-poly(N(ϵ)-((1-carboxy-cis-cyclohexene)-2-carbonyl)-L-lysine) (mPEG-b-PCLL) and cationic doxorubicin (DOX), a model anthracycline antitumor drug, was constructed by electrostatic interaction for directional intracellular drug delivery in malignancy chemotherapy. The PIC micelle kept constant diameter at physiological condition (i.e., pH 7.4), while gradually swelled and finally disassembled at mimicking intratumoral pH (i.e., 6.8) and especially intracellular endo/lysosomal pH (i.e., 5.5). The DOX release from the PIC micelle at pH 7.4 was slow, whereas obviously accelerated at the intracellular acidic condition of pH 5.5. These results should be related to the rapid cleavage of the side amide bond of mPEG-b-PCLL in an acidic environment. The PIC micelle exhibited satisfactory tumor suppression toward the H22 hepatoma-bearing BALB/c mouse model compared with free DOX, which was demonstrated by the upregulated tumor inhibition rate, and the increased necrotic and apoptosis areas in tumor tissue. Furthermore, the enhanced security was also observed in the PIC micelle group in relation to that of free DOX. The above results strongly supported that the acid-sensitive PIC micelle was promising for selective intracellular drug delivery along with upregulated malignancy inhibition.

Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug.

Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter (D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.