Research progress of nanomaterial drug delivery in tumor targeted therapy.

Cancer is one of the most lethal diseases in human society, and its incidence is gradually increasing. However, the current tumor treatment often meets the problem of poor efficacy and big side effects. The unique physical and chemical properties of nanomaterials can target the delivery of drugs to tumors, which can improve the therapeutic effect while reducing the damage of drugs to normal cells. This makes nanomaterials become a hot topic in the field of biomedicine. This review summarizes the recent progress of nanomaterials in tumor targeted therapy.

Analysis of pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence.

BACKGROUND: To investigate the changes in pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence (SUI). METHODS: A retrospective survey was conducted on 922 women aged 20-40 years who received health examinations at the First Affiliated Hospital of Nanjing Medical University between July 2017 and December 2019. The women were split into two groups: those who had SUI (n=87) and those that did not (n=835). Questionnaires and pelvic floor electrical physiological indexes were collected. RESULTS: The mean age of the group of women with SUI was 29.77 years, while the mean age of the group of women with no SUI was 24.49 years. The body mass indexes (BMI) of the women with SUI were significantly higher than those of the women with no SUI. Importantly, the normal rates of type I and II fibers in the women with SUI were obviously lower than those in the women with no SUI. Moreover, the vaginal dynamic pressure in the women with SUI was significantly lower than in the women with no SUI. The study also found that the incidence of SUI in nulliparous women was higher in those aged 30-40 and that both low-weight and obese women had an increased risk of SUI. Type I and type II muscle fibers were more abnormal in the women with SUI than in those with no SUI. In multivariate logistic regression, the ages, BMIs, and type I fiber indexes of nulliparous women were related to SUI. CONCLUSIONS: Nulliparous women have a higher rate of SUI. Compared to women with no SUI, the possible potential risk factors are age (>30 years), higher BMI, and abnormal type I muscle fiber of the pelvic floor.

Prevalence of Stress Urinary Incontinence in Women with Premature Ovarian Insufficiency.

Background: To determine the prevalence of stress urinary incontinence (SUI) and associated factors in women with premature ovarian insufficiency (POI). Materials and Methods: The study included 149 patients with POI and 303 control women without POI. Age, body mass index (BMI), gestational history, time since onset of POI, and status of hormone therapy (HT) for POI were recorded. Results: There was no statistical difference in the mean age, BMI, and parity between the two groups. The prevalence of SUI in the POI group tended to be higher than that in the control group (20.9%, 30/149 vs. 16.2%, 49/303), although not significantly (p = 0.297). About 41.6% (62/149) of patients with POI received HT. Patients with POI and SUI were older (p = 0.018) and had higher BMI (p = 0.007) than women with POI without SUI (p = 0.007). Compared to nulliparas, primiparas were more likely to have SUI (p = 0.046). However, SUI developed irrespective of time since onset of oligomenorrhea/amenorrhea or HT use. Furthermore, regression analysis showed that the prevalence of SUI was higher in women 30-39 years of age (odds ratio [OR] = 3.27, p = 0.002) and older than 40 years (OR = 7.78, p = 0.001). Primiparas (OR = 2.89, p = 0.001) and vaginal delivery (OR = 2.58, p = 0.023) were associated with SUI. Conclusions: The prevalence of SUI was fairly high among patients with POI, and age, parity, and vaginal delivery were the main risk factors. However, duration of POI and HT use had no effect on SUI. Increasing awareness of the importance of urinary system health in this population will improve the quality of life for these women.

Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pHe: 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pHendo: 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer.

The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR). To overcome multidrug resistance (MDR) and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep). First, the polymers poly(l-histidine)-coupled polyethylene glycol-2000 (PHIS-PEG2000) and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG2000) were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2000) or 7pep-DSPE-PEG2000 (7-pep HD micelles). The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX), the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr), which attributed to the synergistic effect of poly(l-histidine)-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the target-ability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug-resistant tumors.