Tumor‐Specific Aptamer‐Conjugated Polymeric Photosensitizer for Effective Endo‐Laparoscopic Photodynamic Therapy

Abstract

Recent advances in medical technology and endo-laparoscopic devices have enabled the treatment of gastrointestinal (GI) cancers to be minimally invasive through endo-laparoscopic photodynamic therapy (PDT). To achieve an efficient regional or endo-laparoscopic PDT, it is necessary to develop a highly target specific photosensitizer (PS) that can be easily treated to the lesion site with endo-laparoscopic device. Here, an ideal polymeric PS is demonstrated for effective endo-laparoscopic PDT. In the synthetic process, conventional PS (i.e., Chlorin e6, Ce6) is conjugated with an Aptamer (i.e., AS1411) targeting nucleolin (also called C23) overexpressed on the cancer cell membrane using a water-soluble polymeric linker (i.e., polyethylene glycol, PEG). The synthesized Aptamer-PEG-Ce6 could target nucleolinoverexpressing tumor cells efficiently and visualize the tumor tissues through optical and fluorescent imaging both in vitro and ex vivo, and effectively kills cancer cells under laser irradiation. Tumor staining with Aptamer-PEG-Ce6 is easily accomplished through endoscopic equipment within a few minutes. Furthermore, after laser irradiation, Aptamer-PEG-Ce6 is found to penetrate deeply into the tumor tissue and induce apoptosis of tumor cells. Taken together, the tumor-specific Aptamer-conjugated polymeric PS developed in this study has great potential as an ideal photomedicine for effective tumor treatment using endo-laparoscopic PDT.

Intelligent Fe–Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen‐Elevated Synergetic Therapy and Bioimaging

“…And the X-ray photoelectron spectrum (XPS) of FeMn-LDH is presented in Figure S4 (Supporting Information), the Mn 2p 3/2 and Mn 2p 1/2 peaks at 634.4 and 654.5 eV demonstrate the presence of Mn 3+/4+ . [69,70] Simultaneously, the Fe 2p 3/2 and Fe 2p 1/2 located at 712.2 and 725.3 eV indicate the Fe is mostly in Fe 3+ oxidation state. [71] And the standard XRD pattern of β-NaGdF 4 (JCPDS No.…”

Nanotechnology in Modern Photodynamic Therapy of Cancer: A Review of Cellular Resistance Patterns Affecting the Therapeutic Response

“…Their small size allows them to be used for both surface biomarker recognition and intracellular targeting. In previous studies, aptamer-NP conjugates have certainly shown better tissue penetration [ 84 , 85 ]. Recently, Kim et al [ 85 ] developed a tumor-specific aptamer-conjugated polymeric PS for treating gastrointestinal cancer using an AS1411 aptamer, which binds to nucleolin on the membrane of cancer cells.…”

“…In previous studies, aptamer-NP conjugates have certainly shown better tissue penetration [ 84 , 85 ]. Recently, Kim et al [ 85 ] developed a tumor-specific aptamer-conjugated polymeric PS for treating gastrointestinal cancer using an AS1411 aptamer, which binds to nucleolin on the membrane of cancer cells. This compound was use in a laparoscopy-based PDT and their results showed enhanced and effective eradication of cancer cells under laser irradiation.…”

Self-luminescent photodynamic therapy using breast cancer targeted proteins

“…For the stability test of Rluc8 (or Rluc8.6) or its fusion proteins, 10 M protein was incubated in 1× PBS (pH 7.4) or undiluted normal mouse serum (Jackson ImmunoResearch, no. 015-000-001) for different time intervals (1,2,4,8,12,24, and 48 hours) at 37°C. The BL intensity of each reaction was measured using a GLOMAX Luminometer (Promega) immediately after treatment with 150 M Co-h.…”

“…In contrast to classical radiation or chemical therapy, PDT is characterized by the selective ablation of malignant cells, high tumor specificity, and minimal invasiveness. To expand its usefulness, many studies on PDT have explored the development of PS drugs alone or in combination with nanoparticle hybrids (3,4), immunostimulants (5,6), and/or other active targeting ligands (7,8). However, despite these achievements, several major challenges posed by the inherent properties of chemical PS drugs, such as in vivo accumulation and light penetration issues, limit their clinical effectiveness.…”