Related Experiment Video
Updated: Mar 14, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth
Jamie C Harris1, Jeannine M Coburn2, Andre Kajdacsy-Balla3
1Department of Surgery, Rush University Medical Center, 1750 W. Harrison St, Suite 785, Chicago, IL, 60612, USA.
Background:
Sarcoma accounts for 20% of solid tumors in children. Surgery has significant morbidity. We hypothesized that delivering chemotherapy directly into tumors through sustained release silk systems could slow tumor growth.
Methods:
Human Ewing sarcoma cells A673 were cultured with vincristine and doxorubicin to determine half maximal inhibitory concentration (IC50). Cells were injected into mouse hind leg to create orthotopic tumors. Tumor volumes were measured using ultrasound. When volume reached >250mm3, interventions included: implantation of drug-free silk foam (Control-F), doxorubicin 400μg foam (Dox400-F), vincristine 50μg foam (Vin50-F), drug-free silk gel (Control-G), vincristine 50μg gel (Vin50-G), or single dose intravenous vincristine 50μg (Vin50-IV). End-point was volume>1000mm3. Kaplan Meier and ANOVA were used.
Results:
IC50 for vincristine and doxorubicin was 0.5ng/mL and 200ng/mL, respectively. There was no difference between Dox400-F [6±1days to end point (DTEP)] and Control-F (5±1.3 DTEP). Vin50-F (12.4±3.5 DTEP) had slower growth compared to Control-F (p<0.001), and there was no difference between Vin50-F and Vin50-IV (14±0 DTEP). Growth was slowest with Vin50-G, 28±10.3 DTEP compared to all other treatment groups (p<0.05).
Conclusion:
Sustained delivery of vincristine inside the sarcoma tumor with silk gel decreased tumor growth. Applying this intratumoral treatment strategy may potentially decrease the extent of surgical excision.
Insights
Sustained release of vincristine chemotherapy via silk gel directly into pediatric sarcoma tumors significantly slowed growth. This intratumoral drug delivery may reduce the need for extensive surgery in treating childhood cancers.
Area of Science:
- Pediatric Oncology
- Biomaterials Science
- Drug Delivery Systems
Background:
- Sarcomas represent 20% of pediatric solid tumors, often requiring surgery with significant morbidity.
- Novel therapeutic strategies are needed to improve outcomes and reduce treatment-related complications in children.
Purpose of the Study:
- To investigate the efficacy of sustained-release chemotherapy delivered via silk biomaterials for pediatric sarcoma treatment.
- To evaluate the impact of intratumoral drug delivery on tumor growth inhibition.
Main Methods:
- Ewing sarcoma cells (A673) were used to establish orthotopic tumors in mice.
- Tumor volumes were monitored, and interventions included silk foam/gel implants with vincristine or doxorubicin, and intravenous vincristine.
- Half maximal inhibitory concentration (IC50) was determined for chemotherapeutic agents.
Main Results:
- Intratumoral vincristine delivered via silk gel (Vin50-G) demonstrated the slowest tumor growth (28±10.3 days to endpoint), significantly outperforming other treatments (p<0.05).
- Silk foam delivery of vincristine (Vin50-F) also slowed tumor growth compared to controls (p<0.001).
- Doxorubicin-loaded silk foam showed no significant benefit over control.
Conclusions:
- Sustained intratumoral delivery of vincristine using silk gel effectively inhibits sarcoma tumor growth in a preclinical model.
- This localized chemotherapy approach holds promise for reducing surgical intervention in pediatric sarcoma treatment.
