Nanocarrier-based drug delivery systems for bone cancer therapy: a review

Prasad, S. Ram; Kumar, T.S. Sampath; Jayakrishnan, A.

doi:10.1088/1748-605x/abf7d5

Cited by 18 publications

(12 citation statements)

References 172 publications

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“…Aln-NCs potentially resolve issues of kidney toxicity, and systemic delivery of Aln-PT-NCs resulted in therapeutic efficacy. In addition, NC-based delivery may confer additional advantages, including increased drug stability, specificity, favorable release kinetics, and reduced side effects compared with conventional drug delivery methods ( 49 ). These results support the continued development of HIF-2α inhibitors, particularly in formulations that will allow for reduced off-target toxicity, to protect against radiation-induced bone loss.…”

Section: Discussionmentioning

confidence: 99%

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells

Guo,

Hoque,

Garcia Garcia

et al. 2023

Sci. Transl. Med.

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Radiotherapy remains a common treatment modality for cancer despite skeletal complications. However, there are currently no effective treatments for radiation-induced bone loss, and the consequences of radiotherapy on skeletal progenitor cell (SPC) survival and function remain unclear. After radiation, leptin receptor–expressing cells, which include a population of SPCs, become localized to hypoxic regions of the bone and stabilize the transcription factor hypoxia-inducible factor-2α (HIF-2α), thus suggesting a role for HIF-2α in the skeletal response to radiation. Here, we conditionally knocked out HIF-2α in leptin receptor–expressing cells and their descendants in mice. Radiation therapy in littermate control mice reduced bone mass; however, HIF-2α conditional knockout mice maintained bone mass comparable to nonirradiated control animals. HIF-2α negatively regulated the number of SPCs, bone formation, and bone mineralization. To test whether blocking HIF-2α pharmacologically could reduce bone loss during radiation, we administered a selective HIF-2α inhibitor called PT2399 (a structural analog of which was recently FDA-approved) to wild-type mice before radiation exposure. Pharmacological inhibition of HIF-2α was sufficient to prevent radiation-induced bone loss in a single-limb irradiation mouse model. Given that ~90% of patients who receive a HIF-2α inhibitor develop anemia because of off-target effects, we developed a bone-targeting nanocarrier formulation to deliver the HIF-2α inhibitor to mouse bone, to increase on-target efficacy and reduce off-target toxicities. Nanocarrier-loaded PT2399 prevented radiation-induced bone loss in mice while reducing drug accumulation in the kidney. Targeted inhibition of HIF-2α may represent a therapeutic approach for protecting bone during radiation therapy.

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Section: Discussionmentioning

confidence: 99%

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells

Guo,

Hoque,

Garcia Garcia

et al. 2023

Sci. Transl. Med.

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“…Bone is composed of inorganic minerals (50-70%), organic matrix (20-40%), and water and fat (10%) [34]. The organic matrix is mainly collagen, which gives value to the elastic resistance of the bone and serves as a substrate for mineral deposition and growth [35].…”

Section: Bone Tissue Targetingmentioning

confidence: 99%

Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics

et al. 2023

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Osteosarcoma, the most common malignant tumor of the bone, seriously influences people’s lives and increases their economic burden. Conventional chemotherapy drugs achieve limited therapeutic effects owing to poor targeting and severe systemic toxicity. Nanocarrier-based drug delivery systems can significantly enhance the utilization efficiency of chemotherapeutic drugs through targeting ligand modifications and reduce the occurrence of systemic adverse effects. A variety of ligand-modified nano-drug delivery systems have been developed for different targeting schemes. Here we review the biological characteristics and the main challenges of current drug therapy of OS, and further elaborate on different targeting schemes and ligand selection for nano-drug delivery systems of osteosarcoma, which may provide new horizons for the development of advanced targeted drug delivery systems in the future.

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“…The two main challenges of bone tumor therapy are repairing large bone defects and eradicating all possible residual tumor cells [11]. Even with currently available aggressive treatments (e.g., extensive surgical resection, chemotherapy, radiotherapy), the outcomes have not considerably improved over the past few decades for osteosarcoma or Ewing sarcoma patients [8,58].…”

Section: Recent Approaches Against Bone Tumorsmentioning

confidence: 99%

“…Bone-targeting carriers combined with the desired drugs or bioactive agents have been extensively investigated to enhance bone healing, while minimizing off-target effects [58,90]. In this respect, recent advances in developing both carrier systems and drug formulations are further presented.…”

Section: Drug Deliverymentioning

confidence: 99%

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

Bădilă

Rădulescu

Niculescu

et al. 2021

Cancers

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In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.

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Nanocarrier-based drug delivery systems for bone cancer therapy: a review

Cited by 18 publications

References 172 publications

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells

Radiation-induced bone loss in mice is ameliorated by inhibition of HIF-2α in skeletal progenitor cells

Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

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