<i>In Vivo</i> Targeted Deep-Tissue Photodynamic Therapy Based on Near-Infrared Light Triggered Upconversion Nanoconstruct

Two major challenges of current photodynamic therapy (PDT) are the limited tissue penetration of excitation light and poor tumor-selectivity of the photosensitizer (PS). To address these issues, we developed a multifunctional nanoconstruct consisting of upconversion nanoparticles (UCNPs) that transform near-infrared (NIR) light to visible light and a photosensitizer zinc(II) phthalocyanine (ZnPc). Folate-modified amphiphilic chitosan (FASOC) was coated on the surface of UCNPs to anchor the ZnPc close to the UCNPs, thereby facilitating resonance energy transfer from UCNPs to ZnPc. Confocal microscopy and NIR small animal imaging demonstrated the enhanced tumor-selectivity of the nanoconstructs to cancer cells that overexpressed folate receptor. Reactive oxygen species (ROS) generation in cancer cells under a 1-cm tissue was higher upon excitation of UCNPs with the 980 nm light than that with 660 nm irradiation. <i>In vivo</i> PDT treatments for deep-seated tumors demonstrated that NIR light-triggered PDT based on the nanoconstructs possessed remarkable therapeutic efficacy with tumor inhibition ratio up to 50% compared with conventional visible light-activated PDT with a noticeable reduced tumor inhibition ratio of 18%. These results indicate that the multifunctional nanoconstruct is a promising PDT agent for deep-seated tumor treatment and demonstrate a new paradigm for enhancing PDT efficacy

MOESM1 of A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

Additional file 1. Questionnaire for survey of the clinical features and management of bone metastatic disease in China

The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients.</p><p>Methods</p><p>We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients.</p><p>Results</p><p>Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02).</p><p>Conclusions</p><p>This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy.</p></div

Forest plot and pooled HR & 95%CI for PFS: Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.

<p>Forest plot and pooled HR & 95%CI for PFS: Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.</p

Forest plot and pooled RR & 95%CI for ORR (left) and DCR (right): Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.

<p>Forest plot and pooled RR & 95%CI for ORR (left) and DCR (right): Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.</p

Forest plot and pooled HR & 95%CI for OS: Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.

<p>Forest plot and pooled HR & 95%CI for OS: Antiangiogenic agents plus single agent chemotherapy versus standard second-line chemotherapy.</p

Qualitative analysis of publication bias: Funnel plot of included studies for all outcome.

<p>(A) OS, (B) ORR, (C) PFS and (D) DCR.</p

Summary of the subgroup results: Pooled HR & 95%CI for OS.

<p>* AT for antiangiogenic-TKI;</p><p>^& AA refers to antiangiogenic antibody;</p><p>^¶ Double TKI means antiangiogenic-TKI plus EGFR-TKI.</p><p>Summary of the subgroup results: Pooled HR & 95%CI for OS.</p

Summary of the pooled results and corresponding details.

<p>Summary of the pooled results and corresponding details.</p

Summary of the subgroup results: Pooled HR & 95%CI for PFS and the corresponding details.

<p>* AT for antiangiogenic-TKI;</p><p>^& AA refers to antiangiogenic antibody.</p><p>^¶ Double TKI means antiangiogenic-TKI plus EGFR-TKI.</p><p>Summary of the subgroup results: Pooled HR & 95%CI for PFS and the corresponding details.</p