Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo

Pathak

Artificial Cells, Nanomedicine, and Biotechnology

et al. 2019

Ovarian cancer is the second most common gynaecological malignancy. It usually occurs in women older than 50 years, and because 75% of cases are diagnosed at stage III or IV it is associated with poor diagnosis. Despite the chemosensitivity of intraperitoneal chemotherapy, the majority of patients is relapsed and eventually dies. In addition to the challenge of early detection, its treatment presents several challenges like the route of administration, resistance to therapy with recurrence and specific targeting of cancer to reduce cytotoxicity and side effects. In ovarian cancer therapy, nanocarriers help overcome problems of poor aqueous solubility of chemotherapeutic drugs and enhance their delivery to the tumour sites either by passive or active targeting, and thus reducing adverse side effects to the healthy tissues. Moreover, the bioavailability to the tumour site is increased by the enhanced permeability and retention (EPR) mechanism. The present review aims to describe the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors designed against ovarian cancer to overcome the drawbacks of conventional delivery. Conclusively, targeted nanocarriers would optimise the intra-tumour distribution, followed by drug delivery into the intracellular compartment. These features may contribute to greater therapeutic effect. ARTICLE HISTORY

Section: Skov-3 Female Balb/c Mice 88mentioning

confidence: 88%

RETRACTED ARTICLE: Nanoscale drug delivery strategies for therapy of ovarian cancer: conventional vs targeted

Pathak

Artificial Cells, Nanomedicine, and Biotechnology

et al. 2019

“…PEG‐PLA block copolymer was synthesized as described elsewhere . Recrystallized lactide (10 g) was added to a vial in argon gas.…”

Section: Methodsmentioning

confidence: 99%

“…2.2 | Preparation of PEG-PLA and FA-PEG-PLA copolymer PEG-PLA block copolymer was synthesized as described elsewhere. 15 Recrystallized lactide (10 g) was added to a vial in argon gas. Then, THF (20 mL), KHMDS (1.5 mL) (initiator), and epoxyethane (2.4 mL) were added to another vial and stirred continuously for 2 days in an ice bath.…”

mentioning

confidence: 99%

Hypocrellin B‐loaded, folate‐conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo

Yao

Wang

et al. 2018

Cancer Science

Self Cite

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)‐poly (lactic acid)(PLA)‐folate (FA‐PEG‐PLA) was prepared in order to synthesize an active‐targeting, water‐soluble and pharmacomodulated photosensitizer nanocarrier. Drug‐loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA‐PEG‐PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA‐PEG‐PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA‐PEG‐PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR−). The enhanced uptake of HB/FA‐PEG‐PLA micelles to cancer cells resulted in a more effective post‐PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA‐PEG‐PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate‐targeted micelles in tumor‐bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20‐fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB‐loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA‐PEG‐PLA micelles have a high drug‐loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

“…2 Approaches for targeting FRs as therapies for cancer and inflammatory diseases. 1) Folate [ 13 ] or Antibody [ 58 ] drug-conjugates [ 59 ], 2) Monoclonal antibodies (immune effector cell engagement): antibodies link FRs-expressing tumor cells with immune effector cells that bear Fc receptors leading to antibody-dependent effector cell-mediated cytotoxicity [ 27 , 29 ], 3) Chimeric antigen receptor (CAR) T cells: CAR T cells recognizing FRs through scFv (single chain variable fragment) trigger tumor cell killing [ 60 – 62 ], 4) Folate or Antibody nanoparticles-conjugates [ 63 ] …”

Section: Folate Receptors For Targeting Tumors and Inflammatory Diseamentioning

confidence: 99%

Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases

Frigerio

Bizzoni

Jansen

et al. 2019

J Exp Clin Cancer Res

Folate receptors and transporters and one-carbon metabolism continue to be important areas of study given their essential roles in an assortment of diseases and as targets for treatment of cancer and inflammation. Reflecting this, every 2 years, the Folate Receptor Society organizes an international meeting, alternating between North America and Europe, where basic and translational scientists, clinical oncologists and rheumatologists from both academia and industry convene in an informal setting. The 7th International Symposium on Folate Receptors and Transporters was held in Sant’Alessio Siculo (ME), Taormina, Italy from 1st to 5th of October 2018, organized by Dr. Mariangela Figini from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Following the format of previous meetings, more than 50 scientists from 9 different countries attended the 2018 meeting to share ongoing developments, discuss current research challenges and identify new avenues in basic and translational research. An important feature of this meeting was the participation of young investigators and trainees in this area, two (A. Dekhne and N. Verweij) of whom were awarded fellowships to attend this meeting as a recognition of the high scientific quality of their work. This report provides a synopsis of the highlights presented in the following sessions: Barton Kamen Lecture; Targeting one-carbon metabolism in cytosol and mitochondria; Structure and biology of the one-carbon solute transporters; Physiology and pathophysiology of folate receptors and transporters; Folate receptors for targeting tumors and inflammatory diseases; Conventional and new anti-folate drugs for treating inflammatory diseases and cancer; Imaging; Ongoing clinical trials; and Chimeric Antigen Receptor cell therapies of cancer.