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. 2020 Mar 19:15:1915-1928.
doi: 10.2147/IJN.S244849. eCollection 2020.

Paclitaxel-Loaded Macrophage Membrane Camouflaged Albumin Nanoparticles for Targeted Cancer Therapy

Xi Cao  1   2 , Tingfei Tan  1   2 , Dongchun Zhu  1   2 , Haixia Yu  1   2 , Yaru Liu  1   2 , Haiyun Zhou  1   2 , Yong Jin  3   4 , Quan Xia  1   2
Affiliations

Paclitaxel-Loaded Macrophage Membrane Camouflaged Albumin Nanoparticles for Targeted Cancer Therapy

Xi Cao et al. Int J Nanomedicine. .

Abstract

Background: Melanoma is the most common symptom of aggressive skin cancer, and it has become a serious health concern worldwide in recent years. The metastasis rate of malignant melanoma remains high, and it is highly difficult to cure with the currently available treatment options. Effective yet safe therapeutic options are still lacking. Alternative treatment options are in great demand to improve the therapeutic outcome against advanced melanoma. This study aimed to develop albumin nanoparticles (ANPs) coated with macrophage plasma membranes (RANPs) loaded with paclitaxel (PTX) to achieve targeted therapy against malignant melanoma.

Methods: Membrane derivations were achieved by using a combination of hypotonic lysis, mechanical membrane fragmentation, and differential centrifugation to empty the harvested cells of their intracellular contents. The collected membrane was then physically extruded through a 400 nm porous polycarbonate membrane to form macrophage cell membrane vesicles. Albumin nanoparticles were prepared through a well-studied nanoprecipitation process. At last, the two components were then coextruded through a 200 nm porous polycarbonate membrane.

Results: Using paclitaxel as the model drug, PTX-loaded RANPs displayed significantly enhanced cytotoxicity and apoptosis rates compared to albumin nanoparticles without membrane coating in the murine melanoma cell line B16F10. RANPs also exhibited significantly higher internalization efficiency in B16F10 cells than albumin nanoparticles without a membrane coating. Next, a B16F10 tumor xenograft mouse model was established to explore the biodistribution profiles of RANPs, which showed prolonged blood circulation and selective accumulation at the tumor site. PTX-loaded RANPs also demonstrated greatly improved antitumor efficacy in B16F10 tumor-bearing mouse xenografts.

Conclusion: Albumin-based nanoscale delivery systems coated with macrophage plasma membranes offer a highly promising approach to achieve tumor-targeted therapy following systemic administration.

Keywords: albumin nanoparticles; macrophage membrane; melanoma; paclitaxel; tumor-targeted therapy.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Size distribution and morphology of nanoparticles: Dynamic light scattering (DLS) size measurement and TEM image of (A) ANPs, (B) membranes, and (C) RANPs. Scale bar represents 100 nm.
Figure 2
Figure 2
Time-dependent cellular uptake of ANPs/Did and RANPs/Did after incubation with B16F10 (A), A549 (B), 4T1 (C)and MCF-7 cells (D) for 0.5 hr, 1 hr, and 2 hrs as determined by flow cytometry analysis. Data represent means ± SD (n = 3). *p < 0.05 vs control. #p < 0.05 vs ANPs/Did.
Figure 3
Figure 3
(A) Representative confocal laser scanning microscopy images of B16F10 cells after incubation with ANPs/Did and RANPS/Did for 0.5 hr, 1 hr, and 2 hrs. DAPI stains for cell nuclei (blue); Did represents NPs or RNPS (red). Scale bar represents 100 µm. (B, C) Internalization pathways of ANPs and RANPs in B16F10 cells. B16F10 cells were preincubated under various conditions, including 4°C, chlorpromazine, verapamil, amiloride, and colchicine. Data represent means ± SD (n = 3). *p < 0.05 vs 37°C.
Figure 4
Figure 4
Representative confocal images of B16F10 cells incubated with coumarin 6-loaded nanoparticles (ANPs/C6 (A) and RANPs/C6 (B)) and LysoTracker Red for 1 hr, 2 hrs, and 24 hrs. Scale bar represents 20 µm.
Figure 5
Figure 5
Time-dependent cellular uptake of ANPs/Did and RANPs/Did after incubation with DCs (A) and RAW 264.7 cells (B) for 0.5 hr, 1 hr, and 2 hrs as determined by flow cytometry analysis. Data represent means ± SD (n = 3). *p < 0.05 vs control. #p < 0.05 vs ANPs/Dids.
Figure 6
Figure 6
Cell viability of B16F10 after 24 hrs of treatment of blank ANPs, blank RANPs, Taxol, ANPs/PTX, and RANPs/PTX with varying concentrations. Data represent mean ± SD (n = 3). *p < 0.05 vs control. #p < 0.05 vs ANPs/Did.
Figure 7
Figure 7
(A) Cell cycle distributions of B16F10 cells after various treatments with equivalent doses of PTX. (B) The apoptotic cell percentages of B16F10 cells after various treatments of blank ANPs, blank RANPs, Taxol, ANPs/PTX, and RANPs/PTX. An equivalent dose of 1 μg/mL PTX was used, and the concentrations of blank nanoparticles were maintained the same as the PTX-loaded nanoparticles. Data represent means ± SD (n = 3). *p < 0.05 vs Taxol, #p < 0.05 vs ANPs/PTX.
Figure 8
Figure 8
Biodistribution profiles of Did-loaded nanoparticles in melanoma xenograft mice. Did-loaded nanoparticles were administered via tail vein injection at an equivalent dose of 0.015 mg/kg. (A) Ex vivo fluorescence imaging of major organs at 1 hr, 2 hrs, and 24 hrs after injection. (B) Ex vivo imaging of blood at given time points. (C) Ex vivo imaging of excised tumors at the given time points.
Figure 9
Figure 9
The antitumor efficacy of PTX-loaded nanoparticles in C57BL/6 mice bearing B16F10 melanoma xenografts. (A) Images of excised B16F10 tumors collected from each treatment. (B) Average tumor volumes after treatment over the investigative period (n = 5). *p < 0.05 vs Taxol, #p < 0.05 vs ANPs/PTX. (C) Bodyweight variations of mice bearing B16F10 melanoma xenografts after each treatment over time. (D) Tumor inhibition rate after treatment. (E) Morphology of RANPs/PTX-treated groups. Sections were isolated and stained with hematoxylin and eosin (H&E) for histopathological analysis. Scale bar represents 100 μm. Data represent means ± SD (n = 5).
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