High-density lipoprotein-biomimetic nanocarriers for glioblastoma-targeting delivery: the effect of shape.

Rational design of the physicochemical properties of nanocarriers can optimize their pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. In particular, particle shape is one of the crucial parameters that can impact the circulation time, tumor accumulation and tumor cell internalization of nanocarrier. Biomimetic reconstituted high-density lipoprotein (rHDL), by mimicking the endogenous shape and structure of high-density lipoprotein, has been indicated as a promising tumor-targeting nanoparticulate drug delivery system whereas the effect of shape on tumor-targeting efficiency has not been fully evaluated. Herein, we constructed apolipoprotein E-based biomimetic rHDL in both discoidal form (d-rHDL) and spherical form (s-rHDL), and compared their efficiency in glioblastoma multiforme (GBM)-targeting delivery. s-rHDL showed higher cellular association in GBM cells especially at a high exposure dosage or after a long incubation time. Moreover, it exhibited deeper penetration in 3D GBM spheroids in vitro and higher accumulation at the GBM site in vivo with the GBM-targeting accumulation of s-rHDL increased by 73% when compared with that of d-rHDL at 24 h post-injection. The findings collectively indicated that s-rHDL might serve as a more efficient nanocarrier for glioblastoma-targeting drug delivery.

Impact of minimally invasive surgery on immune function and stress response in gastric cancer patients.

BACKGROUND: Gastric cancer remains a leading cause of cancer-related mortality globally. Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery. AIM: To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer, focusing on its potential to reduce trauma, accelerate recovery, and achieve comparable oncological outcomes. METHODS: This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023. The patients were divided into two groups: Minimally invasive surgery group (n = 102), who underwent laparoscopic gastrectomy, and open surgery group (n = 101), who underwent traditional open gastrectomy. We compared surgical indicators (surgical incision size, intraoperative blood loss, surgical duration, and number of lymph nodes dissected), recovery parameters (time to first flatus, time to start eating, time to ambulation, and length of hospital stay), immune function (levels of IgA, IgG, and IgM), intestinal barrier function (levels of D-lactic acid and diamine oxidase), and stress response (levels of C-reactive protein, interleukin-6, and procalcitonin). RESULTS: The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators, including smaller incisions, less blood loss, shorter surgery time, and more lymph nodes dissected (P < 0.05 for all). Recovery was also faster in the minimally invasive surgery group, with earlier return of bowel function, earlier initiation of diet, quicker mobilization, and shorter hospital stays (P < 0.05 for all). Furthermore, patients in the minimally invasive surgery group had better preserved immune function, superior intestinal barrier function, and a less pronounced stress response postoperatively (P < 0.05 for all). CONCLUSION: Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function, protecting intestinal barrier function, and mitigating the stress response compared to traditional open surgery. These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis.

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.