Collagen Hybridizing Peptides Conjugated to Water-Soluble Copolymers for Targeting Intratibial Osteosarcoma
21 Oct 2024
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Osteosarcoma (OS) is a common form of malignant bone cancer, often occurring in the ends of long bones. OS is most common in children and teens especially between the ages of 10 and 19, OS manifests in adults in their 60s, 70s or 80s. Treatments typically involve surgery, chemotherapy and radiation. Preoperative chemotherapy has been proven to greatly increase chances of success and reduces the need for limb amputation. Current OS treatments are limited by off-target systemic symptoms impacting quality of life and inoperable tumors increasing changes of amputation. OS patients would greatly benefit from localized delivery of drugs to reduce systemic side effects.
Bone tissue is composed heavily of type I collagen. Collagen provides flexibility to bones while minerals like calcium phosphate make bones hard. OS forms in collagen rich areas of bone, near growth plates and is characterized by collagen remodeling, degradation and invasion into surrounding tissues. These features of OS in the bone make collagen a prime target for localized drug delivery. Collagen hybridizing peptides (CHPs) selectively bind to damaged (remodeling and degrading) collagen in all tissue types, making them a viable candidate for OS drug delivery.
This research explores conjugating CHPs to water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers for tumor targeting and drug delivery. HPMA-CHP conjugate after tail vein injection accumulated at the site of the tumor in vivo at higher concentrations than CHPs alone. Showing HPMA is a reliable copolymer for tumor targeting. Maximum accumulation was reached at six hours and traces of HPMA-CHP conjugates were still detectable at 168 hours. This data suggests targeting damaged collagen for drug delivery may elicit a higher targeted drug exposure in OS tumors.
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