E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Cell Lines
2.3. Tumor Propagation
- Group I: control group, no treatment.
- Group II: treatment with anti-tumor immunomodulator—EcPHL.
- Group III: treatment with Fe-containing magnetic nanoparticles—mNP.
- Group IV: combined treatment—EcPHL plus mNP.
2.4. Tumor Size Measurements
2.5. Biopreparation
2.6. Immunomodulation
2.7. Magnetic Nanoparticles
2.8. Histological Estimation
2.9. Statistical Analysis
3. Results
3.1. Tumor Growth
3.2. Histological Analysis of Mice Tissue
3.2.1. Control: Group I
3.2.2. Group II: Mice Vaccinated with EcPHL Immune Modulator
3.2.3. Group III: EcPHL-Untreated Mice Administered with mNP via Local Intratumor Injection
3.2.4. Group IV: EcPHL- and mNP-Treated Mice
3.3. EcPHL Immunomodulator Treatment Effect
4. Discussion
- (a)
- EcPHL exhibits strong anticancer immunomodulatory properties affecting the TME. The EcPHL efficacy was strongest on the 9th and 12th days of Ehrlich carcinoma growth, after the first and second EcPHL vaccinations, which could be related to the increased ratio of M1/M2 macrophages in the TME [45,46].
- (b)
- Histological analyses of the EcPHL-treated mice tumor tissue samples (see Figure 5, Figure 6, Figure 7 and Figure 8) show an increased number of macrophages (supposedly M1 phenotype), which, in turn, release cytokines (e.g., IL-12, TFN-α, and IFN-γ), stimulate further immune system responses, specifically in and around the tumor lesions, and promote tumor cell killing. The observed EcPHL efficacy and the effect of the macrophages on Ehrlich carcinoma are consistent with the view that M1 macrophages possess anti-tumor properties [24,47,48,49].
- (c)
- Although an increase in the M1/M2 ratio in the TME should provide better clinical outcomes in cancer [46], the balance between M1 and M2 macrophage polarization in the TME is influenced by a range of factors, including cytokines, chemokines, and other signaling molecules produced by tumor cells. Even though, at present, we cannot determine which factors of the exogenous EcPHL vaccine activated M1 macrophages and how they impacted Ehrlich carcinoma growth, we hypothesize that EcPHL overdose can reduce the ratio of M1/M2 macrophage polarization in the TME, and as a result, it can decrease EcPHL vaccination efficacy.
- (d)
- EcPHL improves mNP distributions and the spread radius in the tumor tissue from the local inoculation point in comparison to mice tumor tissue without immunomodulation. The mNP were observed in the necrotic areas and fatty and connective tissues, as well as in the TAMs, both intra- and extracellularly. Intracellular iron-containing exogenous pigments were visible in the cytoplasmic granule. A large number of mNP were observed in inflammatory infiltrates, necrotic areas, and macrophages.
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ghambashidze, K.; Chikhladze, R.; Saladze, T.; Hoopes, P.J.; Shubitidze, F. E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor. Cancers 2023, 15, 2315. https://doi.org/10.3390/cancers15082315
Ghambashidze K, Chikhladze R, Saladze T, Hoopes PJ, Shubitidze F. E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor. Cancers. 2023; 15(8):2315. https://doi.org/10.3390/cancers15082315
Chicago/Turabian StyleGhambashidze, Ketevan, Ramaz Chikhladze, Tamar Saladze, P. Jack Hoopes, and Fridon Shubitidze. 2023. "E. coli Phagelysate: A Primer to Enhance Nanoparticles and Drug Deliveries in Tumor" Cancers 15, no. 8: 2315. https://doi.org/10.3390/cancers15082315