Alendronate-Modified Polymeric Micelles for the Treatment of Breast Cancer Bone Metastasis

Abstract

Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remain high in incidence and challenging to manage. Here we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactantbased formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

The past, present, and future of breast cancer models for nanomedicine development

“…The most widely used syngeneic breast cancer model for the evaluation of nanomedicines is the orthotopic TNBC 4 T1 model [171] , [172] , which exhibits several advantageous characteristics, including the well-vascularized nature of the tumor [173] , the high metastatic capacity in the lungs and lymph nodes [64] , and adequate TME representation [174] .…”

Drug Delivery to the Bone Microenvironment Mediated by Exosomes: An Axiom or Enigma

“…Alendronate (ALN), as a bone homing agent decorated with polymeric micelles encapsulated with docetaxel, has been developed for treating breast cancer bone metastases with better pharmacokinetics and sustained release. 144 However, the major setbacks that micelles possess are the high cost for the preparation of micelles at a large scale and difficulty in loading hydrophilic drugs. 145…”

“…Alendronate (ALN), as a bone homing agent decorated with polymeric micelles encapsulated with docetaxel, has been developed for treating breast cancer bone metastases with better pharmacokinetics and sustained release. 144 …”

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors

“…Liu et al 52 functionalized an amphiphilic triblock copolymer (PEG-PGlu-PPhA) composed of polyglutamic acid, polyphenylalanine and polyethylene glycol with ALN to prepare bone homing polypeptide-based polymer micelles with chemotherapy docetaxel for the treatment modalities to cure bone metastases of breast cancer, which slowed disease progression and improved the survival rate in a syngeneic murine model of breast cancer bone metastasis. Using an immunologically active mouse breast cancer model that spreads to the bones, the study confirmed that targeted micelle-based therapy significantly leads to a reduction in tumor burden and prolongs the survival rate of animals, demonstrating the effectiveness of this targeted strategy for delivering chemotherapy to the bone.…”