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. 2022 Sep 3;23(17):10068. doi: 10.3390/ijms231710068

Table 3.

Summary of different LNPs employed for the treatment of TNBC.

Excipients Results Ref.
Liposomes
1,2-dioleoyl-snglycero- 3-phosphocholine (DOPC)
1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[carboxy (polyethylene glycol)-2000] (DSPE-PEG-COOH)
  • -

    Showed an average particle size of 130 ± 30 nm with a zeta potential of −6 and −10 mV

  • -

    Exhibited an enhanced internalization to TNBC cells with reduced proliferation in vitro, enhanced tumor targetability, and antitumor efficacy with reduced lung metastasis

 [52]
DSPE-PEG2000
  • -

    Exhibited an enhanced cellular uptake by TNBC cells in vitro

  • -

    Modified miRNA liposomes showed enhanced anticancer activity with increased internalization to TNBC cells, and increased inhibitory rates as compared to free miRNA complexes

 [53]
Dioleoylphosphatidylethanolamine (DOPE)
  • -

    ILips facilitate the release of CD-47 and enhanced phagocytosis of TNBC cells and activated the responses of the T cell immune system.

  • -

    ILips showed a lower IC50 compared to paclitaxel-liposomes and free paclitaxel

  • -

    ILips showed an increased expression of CD80 (1.5-fold) as compared to free CD-47

 [54]
Dipalmitoylphosphatidylcholine (DPPC)
Distearoylphosphatidylcholine (DSPC)
Cholesterol
Distearoylphosphatidylethanolamine (DSPE)
  • -

    LipTS–GD–MAB showed increased cellular internalization as compared to doxorubicin liposomes

 [55]
LecithinCholesterol
  • -

    AZD-lipo showed enhanced anti-cancer activity along with increased oral bioavailability as compared to free AZD

  • -

    AZD-lipo showed decreased IC50 values, reduced proliferation of TNBC cells, and angiogenesis in TNBC cells as compared to free AZD

 [56]
Nanoemulsion (NEs)
Cod liver oil
Lysophophatidylcholine (LPC),
lysophophatidic acid (LPA),
DSPE-PEG (2000)
  • -

    DAC/PAN LNEs decreased the cell viability of MDA-MB-231 by 55%

  • -

    DAC/PAN-LNEs synergistically decreased the expression of FOXM1 mRNA and FOXM1 protein expressions by 80%

 [62]
Soya lecithin
Kolliphor® HS15
  • -

    NanoPue reduced the expression of TAFs and enhanced ITLs of cytotoxic T cells by 6-fold and 2-fold respectively as compared to control

 [63]
Soybean phospholipids
Cholesterol
  • -

    NE reduced the stabilization of HIF-1α by effectively scavenging ROS.

  • -

    NE limited angiogenesis and NLRP3 inflammasomes and IL-1β

 [64]
Miglyol 812
Phosphatidylcholine
  • -

    NEs decreased tumor growth and cell proliferation in vitro and in vivo.

  • -

    ET-NEs showed a dose-dependent IC50 which was found to be 6.9 μg/mL at 13.2 μM after 24 h of incubation, whereas the free ET showed a higher IC50 which is 13.9 μg/mL at 26.5 μM

 [65]
Solid lipid nanoparticles (SLNs)
GMS (Glyceryl monostearate)
Tween 80
  • -

    BMN 673-SLNs induced significant toxicity in TNBC cells

 [75]
Palmitic acid
Pluronic F-68
Soy lecithin
  • -

    DADS-RAGE-SLNs significantly increased the cytotoxicity, apoptosis and cellular internalization as compared to DADS

 [76]
GMS
SA (Stearic acid)
Compritol ATO 888
Tween 80 as a surfactant
  • -

    DTX-ALA-SLNs showed increased cytotoxicity to 4T1 cells as compared to DTX-SLNs, ALA-SLNs, and free drugs

  • -

    Also, DTX-ALA SLNs showed increased apoptosis of 32% as compared to free DTX which is only 11%

 [77]
Stearyl amine
Tween 80,
Pluronic F-68
  • -

    Niclo-SLNs showed increased cytotoxicity and enhanced cellular internalization at the G0/G1 phase of the cell cycle as compared to free Niclo

 [78]
  • -

    PBA-Niclo-SLNs showed increased cytotoxicity, inhibition of cell proliferation at G0/G1 cell cycle and apoptosis as compared to Niclo-SLNs and free Niclo respectively.

  • -

    PBA-Niclo-SLNs significantly inhibited STAT3, TNBC stem cell populations, and EMT markers

 [79]
Nanostructured lipid carriers (NLCs)
Compritol ATO 888
Medium chain triglycerides (MCT)
Tween 80
Soya lecithin
  • -

    PTX-NLCs showed increased in-vitro cell cytotoxicity and anti-clonogenic activity against MDA-MB-231 cells as compared to free PTX

  • -

    PTX-NLC exhibited 1.5 and 1.7-fold increased tumor site accumulation after 30 and 120 min respectively in tumor-bearing mice, as compared to free PTX

 [81]
Precirol ATO 5
Maisine 35-1
Cremophor RH40
  • -

    FA-PTX-Ce6-NLC showed enhanced MDA-MB-231 cellular uptake as compared to free PTX

  • -

    NLC system also showed enhanced drug-loading without side effects as compared to free PTX

 [82]
Compritol 888 ATO
Docosahexaenoic acid (DHA)
Tween 80
  • -

    NLCs showed a controlled release profile with an increased release in acidic media

  • -

    NLCs exhibited decreased mortality in mice, reduced metastasis to lungs, prevented drug-induced toxicity to vital organs

 [83]
GMS
Caproyl 90
Labrasol
  • -

    RVT-NLC showed decreased cell-viability and increased therapeutic efficacy as compared to free RVT

  • -

    Further, RVT-NLCs loaded microneedle showed increased skin permeation, improved cellular internalization, increased pharmacokinetic attributes and prevented metastasis as compared to free RVT

 [84]
GMS
Caproyl 90
Poloxamer 188
  • -

    LTN-CS-NLC exhibited a slow-release profile of LTN during a 24 h study with increased mucoadhesion, improved gastrointestinal stability, and intestinal permeation as compared to free LTN.

  • -

    Moreover, LTN-CS-NLC showed decreased MDA-MB-231 cell viability as compared to free LTN after 48 h treatment

 [85]
Lipid– Polymer hybrid nanoparticles (LPH-NPs)
HPESO (hydrolyzed polymer of epoxidized soyabean oil)
Myristic acid
  • -

    RGD-DMPLN increased cytotoxicity, cellular accumulation, restricted lung metastasis (31-fold), decreased toxicity to the liver and heart, and improved median survival time (57%)

 [87]
Poly lactide glycolic acid (PLGA)
Polyethylene glycol (PEG)
Dioleoylphosphatidic acid (DOPA)
  • -

    LPH-NPs decreased the cell viability by approximately 80% as compared to free paclitaxel at the same dose of 0.67 μg/mL

  • -

    Moreover, LPH-NPs showed enhanced intracellular activity as compared to free paclitaxel

 [88]
Gelucire 48/16,
Phospholipid 90NG
Phospholipid S100
  • -

    LPH-NPs exhibited rapid cellular internalization within 2 h, showed 10-fold increased bioavailability, ~21–25% less tumor cell growth, and 5–6 times increased MRT as compared to free drugs

 [89]
PLGA,
DSPE-PEG
Lecithin
  • -

    CuB-NPs showed decreased cell viability, increased apoptosis as compared to free CuB

 [90]
Exosomes (Exo)
Mesenchymal stem cells (MSCs),
Surface proteins: tetraspanins (CD63, CD9, CD81), heat shock proteins (Hsc70), lysosomal proteins (Lamp2b), and fusion proteins (flotillin, annexin).
  • -

    MSCs-Exo efficiently delivered anti-miR-142-3p to TNBC cells

  • -

    Increased the transcription of the regulatory target genes.

  • -

    MSCs-Exo exhibited enhanced penetration to cancer cells.

 [101]
Human monocyte-derived macrophage cells
Surface proteins (Exosomal marker proteins): CD81 and CD63.
  • -

    A15-Exo co-loaded with Dox and Cho-miR159 exhibited synergistic therapeutic activity.

  • -

    miR159 and Dox delivery effectively silenced the TCF-7 gene and showed enhanced anticancer effects, without any adverse effects

 [102]
Human fetal lung fibroblast
Surface proteins (Exosomal markers): TSG101 and CD81
  • -

    Erastin@FA-exo showed increased cellular uptake compared to free erastin.

  • -

    Moreover, showed better inhibitory effect on the proliferation and migration of TNBC cells.

  • -

    Erastin@FA-exo showed enhanced ferroptosis with intracellular depletion of glutathione and ROS production.

 [103]
Macrophage
Surface proteins
  • -

    Engineered exosome coated nanoparticles exhibited increased cellular uptake and enhanced antitumor efficacy compared to free Dox and Dox loaded polymeric nanoparticles.

  • -

    Moreover, engineered exosome coated nanocarriers demonstrated remarkable tumor-targetability that further led to significant inhibition of tumor growth and tumor apoptosis.

 [104]