Amphiphilic Zwitterionic Bioderived Block Copolymers from Glutamic Acid and Cholesterol : Ability to Form Nanoparticles and Serve as Vectors for the Delivery of 6-Mercaptopurine

In this work, the straightforward synthesis of amphiphilic zwitterionic bioderived block copolymers (BCPs) using glutamic acid (Glu) and cholesterol (Chol) as building blocks are reported. The previously established Glu-derivative NBoc-Glu-OtBu-methacrylate (NBoc-Glu-OtBu-MA) serves as hydrophobic precursor for the zwitterionic block, while a mostly unexplored cholesteryl-derived methacrylate monomer (Chol-MA) with increased side chain flexibility functions as the hydrophobic block. In the first step, NBoc-Glu-OtBu-MA is polymerized via reversible addition-fragmentation chain-transfer (RAFT) polymerization. Afterward, the linear polymer is chain-extended with Chol-MA, yielding P(NBoc-Glu-OtBu-MA)(n)-b-(Chol-MA)(m) BCPs with varying block ratios. After deprotection under acidic conditions, polymers with a block weight ratio of 87:13 (Glu-OH-MA:Chol-MA) readily assemble into polymeric nanoparticles (NPs) of a desirable size below 100 nm diameter, making them good candidates for biomedical applications. The experimental results are supported using computations of the partition coefficients and machine learning models for the prediction of the polymer densities of the different BCPs. In addition, high (up to 20 wt.%) loading of the hydrophobic anti-cancer drug 6-mercaptopurine (6-MP) is achieved in these NPs during the assembly process. The cytostatic activity of 6-MP NPs is demonstrated in vitro on MDA-MB-231 breast cancer cells. These results emphasize the potential of amphiphilic zwitterionic bioderived NPs for the delivery of hydrophobic drugs

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care.Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests.Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer.</p

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care.Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests.Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer.</p