## 7 Nanomedicine to Enhance the Therapeutic Effectiveness of BC
### Nanotechnology to Enhance Immunotherapy for BC Treatment  
Immunotherapy offers a hopeful avenue in cancer treatment, featuring various methods such as checkpoint inhibition and cellular therapies. While some patients have seen remarkable results, only a limited number benefit long-term, especially for specific cancer types. A deeper comprehension of the interrelations between the immune system of the host and tumors is necessary to broaden the advantages of immunotherapy. The exploration of nanotechnologies for immunotherapy delivery involves utilizing nanoparticles to carry immune-boosting or immune-altering molecules, combined with chemo- or radiotherapy or as supplements to other immunotherapies. Separate nanoparticle vaccines are in development to enhance the T-cell response to eliminate tumors. This can be achieved by codelivering antigens and adjuvants, incorporating various antigens for stimulating  
Figure 5: Applications of nanomaterials in drug delivery systems. (**a**) Doxorubicin-, curcumin-, and perfluorooctyl bromide-loaded PLGA NPs for treatment of BC [115], reproduced with permission from [PERSON] et al., (2018), Creative Commons Attributions 4.0; (**b**) methotrexate-modified Au @PDA-PEG NPs for improved photothermal therapy and chemotherapy for BC [116], reproduced with permission from [PERSON] et al., (2021), Creative Commons Attributions 4.0; (**c**) ejurubicin-encapsulated carbon nanoparticles for tracing and as a local chemotherapeutic on breast cancer with axillary metastasis [117], reproduced with permission from [PERSON] et al., (2016), Creative Commons Attributions 4.0; (**d**) 5-fluorouracilouncil-incorporated PLG nanoparticles for slower drug release toward various cancer cell lines, including BC cell lines [118], reproduced with permission from [PERSON] et al., (2023), Creative Commons Attributions 4.0; (**e**) paclitaxel liposomal nanoformulations for TNBC treatment [119], reproduced with permission from [PERSON] et al., (2021), Creative Commons Attributions 4.0.  
multiple dendritic cell targets, and maintaining a steady release of antigens for extended immune activation [120]. Nanotechnology's role in immunotherapy also encompasses the placement of immune depots within or close to tumors for on-site vaccination and the creation of synthetic antigen-presenting cells [121]. Numerous attempts have been made to enhance antitumor immunity through immune modulation. Nanomaterials have gained substantial attention for their capacity to tackle current problems in cancer immunotherapy. In a notable approach, the Toll-like receptor 7/8 agonist, which is a small immunomodulatory molecule, was chemically bonded to a biodegradable polymeric nanoparticle for use in treating metastatic breast cancer alongside PD-1 checkpoint blockade immunotherapy [122]. The nanoparticle treatments demonstrated a notable absence of toxicity typically associated with the direct use of resiquimod. This suggests that embedding resiquimod into nanoparticles reduced the toxicity concerns, making these nanoparticles potential candidates for clinical application [122]. A combined immunotherapy system utilizing the recombinant Nap protein from _Helicobacter pylori_ was developed for breast tumor therapy [123]. Chitosan nanoparticles, which are pseudo-spherical and positively charged, were engineered to transport HP-Nap. In vitro experiments were conducted on mice (4T1) and human (MCF7) BC cell lines. In vivo, testing occurred on mice with 4T1 tumors. Both TUNEL assays and real-time PCR tests were executed on tumor-bearing mice postnanoparticle therapy [124]. In vivo, tests on female BALB/c mice showcased reduced tumor size after receiving the HP-Nap-loaded nanoparticle treatment. The TUNEL assay also indicated cell death in retrieved mouse BC cells [123]. A decline in the expression of VEGF and MMP9 genes in 4T1 cells was confirmed by real-time PCR. This evidence implies the nanocomplex might reduce mouse tumor growth by modifying cytokine production and amplifying the immune system's tumor-killing actions [123].