Drug delivery nanocarriers and recent advances ventured to improve therapeutic efficacy against osteosarcoma: an overview

Abstract

Background Osteosarcoma (OS) is one of the key cancers affecting the bone tissues, primarily occurred in children and adolescence. Recently, chemotherapy followed by surgery and then post-operative adjuvant chemotherapy is widely used for the treatment of OS. However, the lack of selectivity and sensitivity to tumor cells, the development of multi-drug resistance (MDR), and dangerous side effects have restricted the use of chemotherapeutics. Main body There is an unmet need for novel drug delivery strategies for effective treatment and management of OS. Advances in nanotechnology have led to momentous progress in the design of tumor-targeted drug delivery nanocarriers (NCs) as well as functionalized smart NCs to achieve targeting and to treat OS effectively. The present review summarizes the drug delivery challenges in OS, and how organic nanoparticulate approaches are useful in overcoming barriers will be explained. The present review describes the various organic nanoparticulate approaches such as conventional nanocarriers, stimuli-responsive NCs, and ligand-based active targeting strategies tested against OS. The drug conjugates prepared with copolymer and ligand having bone affinity, and advanced promising approaches such as gene therapy, gene-directed enzyme prodrug therapy, and T cell therapy tested against OS along with their reported limitations are also briefed in this review. Conclusion The nanoparticulate drugs, drug conjugates, and advanced therapies such as gene therapy, and T cell therapy have promising and potential application in the effective treatment of OS. However, many of the above approaches are still at the preclinical stage, and there is a long transitional period before their clinical application.

Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment

“…In SCID mouse xenograft models, the anticancer efficacy of a mAb anti-CD166 conjugation to DOX-loaded liposomal nanoparticles targeting CD166 in OS cell lines was investigated in vivo. When compared to non-targeted medicines, these antibody-targeted medications demonstrated an increase in cytotoxicity for OS cells (7,13).…”

“…Through SELEX, a repetitive in vitro process of sequential selection and amplification steps, aptamers could be selected from DNA or RNA libraries and function like "chemical antibodies". They are excellent candidates for targeted delivery of therapeutic agents due to their high selectivity and specificity, low immunogenicity, ease of synthesis with low cost and high reproducibility, relatively rapid tissue penetration with no toxicity (52,53); As a result, they are typically utilized in conjunction with anticancer medications to target tumor cell surfaces (7), which may result in more promising outcomes when compared to aptamer-free competitors. Aptamer-drug conjugates (ApDCs) are an efficient technique of reducing OS growth in vitro and in vivo due to advances in technology (54).…”

“…Chemotherapy, followed by total surgical resection and then post-operative adjuvant chemotherapy as well as radiotherapy, is currently the standard treatment strategy for OS. Methotrexate (MTX), doxorubicin (DOX), cisplatin (CDDP), ifosfamide (IFO), and etoposide are commonly used chemotherapeutic agents recommended by The National Comprehensive Cancer Network guidelines, which increased the survival rate in patients with localized resectable tumors by up to 60-70% (1); However, most clinical applications of chemotherapeutics for patients with advanced and metastatic OS have been limited due to a lack of selectivity and sensitivity to tumor cells, toxicity towards normal cells, multidrug resistance (MDR), poor pharmacokinetic performance (6), and other factors that limit treatment efficacy and result in severe adverse effects on vital organs (7). With these combination therapy, the overall 5-year survival percentage for individuals with primary metastatic or relapsed cancer is less than 20% (8).…”

“…Drugs might be delivered to tumor sites by receptormediated endocytosis once the individual ligands have contacted the corresponding tissue in vivo, allowing for tailored distribution of unique effector molecules while reducing adverse effects (12). Ligands such as antibodies, aptamers, peptides (13), saccharide, vitamin, bisphosphonates (BP) (14,15), hyaluronic acid (HA) (16) and folate (17) have been reported to be used in the development of OS targeted drug delivery systems that mediate delivery vehicle and drug interactions with and internalization into OS cells with high specificity and efficiency (7). Some of them have a strong affinity for hydroxyapatite and can be employed as ligand in bone (7).…”

“…Ligands such as antibodies, aptamers, peptides (13), saccharide, vitamin, bisphosphonates (BP) (14,15), hyaluronic acid (HA) (16) and folate (17) have been reported to be used in the development of OS targeted drug delivery systems that mediate delivery vehicle and drug interactions with and internalization into OS cells with high specificity and efficiency (7). Some of them have a strong affinity for hydroxyapatite and can be employed as ligand in bone (7). In terms of drug carrier, liposomes which Alec D. Bangham developed in 1965, served as the first therapeutic nanoparticles to receive FDA approval, are now the most widely used (18).…”