Table 3 The application of macrophage-coated nanoparticles

Cancers

Breast

RAW264.7

CuS

PTX

In vitro: 4T1

In vivo: 4T1

1. Dual anticancer action (PTT) and chemo)

2. Deep tumor penetration

3. Excellent tumor accumulation and retention

[33]

BMMs

-

-

In vitro: 4T1

In vivo: 4T1 and B16F10

1. Programmable cellular vesicle

2. Recognize and interact with CTCs

3. Cancer immunotherapy

[81]

RAW264.7

PLGA

siRNA

In vitro: 4T1

In vivo: 4T1

1. Combine immune-metabolic and immune checkpoint inhibitors

2. pH-responsive platform

3. Improve the endo-lysosomal escape

4. Hybrid biomimetic membrane

[72]

RAW264.7

Gold

DOX

In vitro: 4T1

In vivo: 4T1 and B16F10

1. M1 macrophage membrane

2. Size-changeable

3. Prolong circulation retention properties

4. Cancer immunotherapy

[145]

RAW264.7

PLGA

DOX

In vitro: 4T1

In vivo: 4T1

1. Hybrid membrane

2. Accumulate at sites of inflammation

3. Target specific metastasis

4. Homogenous tumor targeting abilities

[40]

RAW264.7

PLGA

Saikosaponin D

In vitro: 4T1 and MCF-7

In vivo: 4T1

1. Macrophage membrane hybridized with T7 peptide

2. Anti-angiogenesis

[68]

RAW264.7

Liposome

Emtansine

In vitro: 4T1

In vivo: 4T1

1. Improve specific metastasis targeting capability

2. Enhance cellular uptake by 4T1 cells

[35]

RAW264.7

Liposome

DOX

In vitro: 4T1

In vivo: 4T1

1. Bio-imagining

2. Anti-metastasis

3. Evade the immune system’s response

[53]

Mouse peritoneal macrophage

-

PTX

In vitro: MDA-MB-231

In vivo: orthotopic tumor model

1. Tumor homing

2. Step-by-step controlled drug release

3. Cascade-responsive polymeric nanoparticles

[67]

RAW264.7

Bi₂Se₃

Quercetin

In vitro: 4T1

In vivo: 4T1

1. Prolong circulation life

2. Enhance tumor-itropic accumulation

3. Minimal side effect

4. PTT and chemo

[146]

RAW264.7

Mesoporous silica

DOX

In vitro: NIH/3T3

In vivo: 4T1

1. Good stability in vivo

2. Reduce retention RES organs and prolong blood-circulating time

3. Effective accumulation in tumors

[14]

RAW264.7

UCNPs

-

In vitro: MCF-7

In vivo: MCF-7

1. Effective cancer targeting

2. Cancer imaging

3. Good in vivo biocompatibility

[147]

THP-1

Chitosan

-

In vitro: hela, MDA-MB-231 and MCF-7

In vivo: 3D tumor spheroids of Hela

1. Membrane-bound TNF-α

2. Excellent biocompatibility

3. Innate anti-cell proliferative

[148]

Tumor-associated macrophage

UCNPs

Rose Bengal

In vitro: MCF-7 and 4T1

In vivo: 4T1

1. Enhanced biocompatibility and immune compatibility

2. Competitive inhibition

3. A promising immunotherapeutic agent

[75]

RAW264.7

Liposome

DOX

In vitro: 4T1

In vivo: 4T1-luc cells

1. Maximally reduce side-effects

2. pH-sensitive prodrug

3. Enhance therapeutic efficacy

[149]

RAW264.7 derived exosome

AA-PEG

PTX

In vitro:3LL-M27

In vivo: 3LL-M27

1. High loading capacity

2. Exosome modified with AA-PEG

[84]

J774A.1 derived exosome

Liposome

DOX

In vitro: 4T1, K7M2, NIH/3T3

In vivo: -

1. High colloidal stability

2. pH-sensitive sustained drug release

3. Tumor-targeted drug delivery

[150]

RAW264.7

-

DOX

In vitro: 4T1

In vivo: 4T1

1. Definite tumor homing ability

2. Macrophage incubate with DOX solution

3. Treat lung metastasis

[151]

RAW264.7 derived exosome

Liposome

DOX

In vitro: T11 and MDA-MB-231

In vivo: T11 and MDA-MB-231

1. High drug loading

2. Efficient accumulation in triple negative breast cancer cells

3. High anticancer efficacy

[152]

C57Bl6 IC21 macrophages or Balb/c RAW264.7 macrophages

Lipoplex

siRNA

In vitro: 4T1, MDA-MB-231 and 3LL

In vivo: MDA-MB-468

1. Deliver nucleic acids into solid tumor

2. Accumulate at breast cancer

3. Incubation method

[153]

M1 macrophage derived exosome

-

PTX

In vitro: 4T1

In vivo:4T1

1. Immunological-chemo therapy

2. M1 macrophage exosome

3. High antitumor effects

[71]

RAW264.7

Liposome and Gold nanorods

DOX

In vitro: 4T1

In vivo: 4T1

1. PTT and chemotherapy

2. Enhance tumor penetration and coverage

3. Enhance the therapeutic therapy

[154]

RAW264.7

FeO

Carbonic anhydrase IX

In vitro: 4T1

In vivo: 4T1

1. Chemo-dynamic therapy

2. Tumor microenvironment remodeling

3. Prolong the blood circulation time

[155]

RAW264.7

Prussian blue

Hydroxychloroquine

In vitro: 4T1

In vivo: 4T1

1. Macrophage repolarization

2. Reduce RES uptake

3. Enhance tumor accumulation

[156]

RAW264.7

Gold and silica

-

In vitro: 4T1

In vivo: 4T1

1. PTT

2. Long circulation

3. Good colloidal stability

[62]

Bone marrow derived macrophages

PLGA

UCNPs

In vitro: NIH/3T3 and 4T1

1. Bio-imaging

2. Deep penetration

3. NIR-response

[74]

RAW264.7

Chlorin e6

PTX

In vitro: 4T1

In vivo: 4T1

1. Shape changeable nanomedicine

2. Sustain release drugs

3. Induce immunogenic cell death

4. PDT

[157]

Skin

J774A.1

MOF-derived mesoporous carbon

Doxycycline hydrochloride, acetylsalicylic acid, PTX

In vitro: SCC-7

In vivo: SCC-7

1. Enhanced drug loading capacity

2. Evade the mononuclear phagocyte system

3. Autofluorescence-free persistent luminescence imaging

[158]

RAW264.7

Albumin

PTX

In vitro: B16F10

In vivo: B16F10

1. Enhanced cytotoxicity and apoptosis rates

2. Prolong blood circulation

3. Selective accumulation at tumor site

[54]

J774.1

THP-1

Nano-porous silicon

DOX

In vitro: MDA-MB-231

In vivo: MDA-MB-231

1. Enhanced circulation time

2. Improved accumulation in tumor

3. Evade the immune system

4. Cross the biological barriers

[80]

Prostate

RAW264.7

Graphene

DOX

In vitro: RM-1

In vivo: RM-1

1. Effective combination of chemotherapy and PTT

2. Active targeting of tumor cells

3. Stimuli-releasee triggered by NIR

[79]

Cervix

THP-1

SiO₂

-

In vitro: Hela

1. PTT

2. Enhance tumor penetration

3. Achieve good biocompatibility

[87]

Lung

J774A.1

-

DOX

In vitro: HUVEC

In vivo: LL/2

1. Favorable accumulation properties into the lungs

2. No observable acute side effects

3. Simple fabrication protocol

[82]

mouse peritoneal macrophage

Liposome

DOX

In vitro: A549

In vivo: A549

1. Time-controlled release of drug

2. Targeted tumor site

3. Effective therapeutic efficacy

4. Imaging capacity

[85]

Liver

RAW264.7

CuS

sorafenib

In vitro: HepG2

In vivo: H22

1. Selectively accumulation both in vitro and in vivo

2. Combination of PTT and chemotherapy

3. Inhibit tumor cell proliferation and angiogenesis

[88]

Osteosarcoma

RAW264.7

PLGA

PTX

In vitro:143B

In vivo:143B

1. Inflammatory chemotaxis

2. Reduce immune clearance

3. Targeted chemotherapy of osteosarcoma

[159]

Anti-microorganism

Antibacterial

J774

PLGA

-

In vitro: murine TLR4 reporter cells

In vivo: escherichia coli

1. Bind and neutralize endotoxins

2. Sequester proinflammatory cytokines

[94]

Antiparasite

RAW264.7

-

Amphotericin B

In vitro: infected macrophage by L. donovani

1. Deliver drug to the infected tissues

2. Improved the toxicity profile

3. Lowered LD50 value

[105]

Antibacterial

RAW264.7

Gold-silica

-

In vitro: S. aureus

In vivo: S. aureus

1. Targeted bacteria more efficiently

2. Prolonged blood circulation time

3. Excellent biocompatibility

4. Combine with PTT

[97]

Antibacterial

J774 derived exosomes

Liposome

-

In vitro: mouse pulmonary vein endothelial cells

In vivo: LPS-induced sepsis model

1. No effect with endothelial cells

2. Decrease proinflammatory genes but anti-inflammatory 3. Regulate the inflammatory response in target cells

[95]

Antibacterial

J774

PLGA

-

In vitro: J774

In vivo: P. aeruginosa

1. Clear pathogens

2. Natural affinity for virulence factors

3. Neutralize both hemolytic and cytotoxic activities

4. Inherently multi-antigenic and safe for in vivo administration

[96]

Antibacterial

RAW264.7

Ca₃(PO₄)₂-Fe₃O₄

-

In vitro: S. aureus; Escherichia coli; MRSA

In vivo: MRSA

1. Reserved the integrality of membrane structure

2. Superior properties of recognition and adsorption with bacteria, toxins and inflammatory cytokines

3. Better antibacterial and anti-inflammatory abilities

4. Enhance the tissue repair process

[160]

Antiviral

THP-1 or BMMs

-

-

In vitro: hepatitis C from patients

In vivo: hepatitis C from patients

1. Long-lasting inhibitory effects on HCV

2. High uptake of omega-6pufas

3. Sufficient adaptive immune responses

[161]

Antiviral

Alveolar macrophages

PLGA

-

In vitro:

In vivo: murine hepatitis virus A-59

1. Block coronavirus from host cell entry

2. Absorb proinflammatory cytokines

3. Combine with PTT to disrupt virus

4. Alleviate infection progression and reduce transmission risk

[36]

Antiviral

THP-1

PLGA

Lopinavir

In vitro: virus infected A549

model

In vivo: mouse hepatitis virus

1. Neutralize multiple proinflammatory cytokines

2. Suppress the activation of macrophages and neutrophils 3. Significant targeted ability to inflammation sites

4. Superior therapeutic efficacy

[102]

Antiviral

Human monocyte-derived macrophage

Liposome

Indinavir, ritonavir, atazanavir, efavirenz

In vitro: monocyte-derived macrophage with HIV-1

1. Prolonged plasma drug concentrations

2. Slow and steady drug release

3. Targeted delivery to infected sites

4. Reduced toxicity

[51]

Antiviral

BMMs

Liposome

Indinavir

In vitro: HIV

In vivo: HIV-infected humanized immune-deficient mice

1. Promote sustained “local” drug release more than 2 weeks

2. Robust lung, liver, and spleen distribution

3. Induce CD^4 + T-cell protection

[56]

Antibacterial

RAW264.7

Gold

Resolvin D1

In vitro: RAW264.7

In vivo: femoral defect model

1. LPS-pretreated membrane

2. Inhibit proinflammation and promote antiinflammation

3. M2 macrophage repolarization

[162]

Antiviral

BMMs

Liposome

Indinavir

In vitro: HIV-1 infected macrophage

In vivo: HIV-1 encephalitis rodent model

1. Readily penetrate the BBB and enhance brain drug distribution

2. Target to disease sites of viral replication and neuroinflammation

3. Improved antiviral efficacy

[101]

Antibacterial

Peritoneal macrophages

Polymer

-

In vitro: peritoneal macrophages

In vivo: sepsis model

1. Reduce the pro-inflammatory cytokines levels

2. Suppress nitric acid, iNOS, and COX-2

3. Increase the medical product for patients who affected sepsis

[163]

Cardiovascular Diseases

Atherosclerosis

THP-1

-

Catalase

In vitro: HUVEC

In vivo: -

1. Specificity targeted to damaged endothelial cells

2. Easily fabricated in biological conditions and keep antioxidants active

3. Consume ROS

[164]

RAW264.7 derived M2 exosomes

-

hexyl 5-aminolevulinate hydrochloride

In vitro: HUVEC

In vivo: acute peritonitis mouse model

1. AS imaging ang therapy

2. Molecularly engineered M2 macrophage-derived exosome

[116]

RAW264.7 derived exosomes

Polymer

Rapamycin

In vitro: HUVEC, RAW264.7 and smooth muscle cells

In vivo: embryos from zebrafish

1. Favorable hydrodynamic size with negative surface charge

2. ROS-responsive drug release

3. Effectively escape from macrophage uptake

4. Targeted to inflammatory endothelial cells

5. Nontoxic both in vitro and in vivo

[114]

RAW264.7

Polymer

Atorvastatin

In vitro: HUVEC and RAW264.7

In vivo: ApoE^−/− mice

1. Avoid the clearance from the reticuloendothelial system

2. Lead NPs to the inflammatory tissues

3. ROS-responsiveness of NPs enables payload release

4. Sequesters proinflammatory cytokines to suppress local inflammation

[112]

RAW264.7

Fe₃O₄

-

In vitro: H9C2 cells

In vivo: atherosclerosis model

1. High biosafety

2. Effectively target early atherosclerotic lesions

3. Bioimaging by MRI

[110]

RAW264.7

PLGA

Rapamycin

In vitro: HUVEC, smooth muscle cells and RAW264.7

In vivo: ApoE^−/− mice

1. Good biocompatibility

2. Inhibit the phagocytosis by macrophages

3. Targeted endothelial cells and accumulated in as lesions

4. Favorable safety performance

[111]

RAW264.7

PLGA

Colchicine

In vitro: HUVEC and RAW264.7

In vivo: vulnerable atherosclerotic plaque mice

1. Target endothelial cells and escape the endocytosis of macrophage

2. Reduce the lipid plaque load and improve the plaque stability

[115]

Vascular intimal hyperplasia

RAW264.7

Polymer

Rapamycin

In vitro: vascular smooth muscle cells

In vivo: carotid artery wire injury mouse model

1. Innate “homing” capacity

2. Avoid clearance by the immune system

3. Effectively the solubility of rapamycin

4. ROS accumulated for controlling local cargo release

5. Reduce toxic side effects

[165]

Myocardial ischemia/reperfusion injury (MI/RI)

RAW264.7

Polydopamine

-

In vitro: hypoxia/reoxygenation (H/R) model primary neonatal rat cardiomyocytes

In vivo: MI/RI model

1. Target the infarcted myocardium

2. Effectively relieved the MI/RI-induced oxidative stress

3. Inhibit cell pyroptosis by suppressing the NLRP3/caspase-1 pathway

[66]

Hepatic ischemia-reperfusion injury

RAW264.7

PLGA

-

In vitro: RAW264.7

In vivo: rat liver transplantation model

1. Neutralized endotoxin and suppressed the secretion of inflammatory factors

2. Effectively alleviate MI/RI induced by liver transplantation

[166]

CNS

PD

RAW264.7 derived exosome

PLGA

Catalase

In vitro: PC12

In vivo: mouse model of PD

1. High loading efficiency

2. Sustained release

3. Readily taken up by neuronal cells

4. Significant neuroprotective effects in in vitro and in vivo

[125]

PD

BMMs

Polymer

Catalase

In vitro: mouse catecholaminergic CATH.a neurons

1. Targeted therapeutic tissue-specific delivery

2. Sustained release of catalase and to enter the brain

3. Protect nigrostratial neurons

4. Increase BBB penetration and ROS decomposition

[126]

PD

BMMs

Polymer

Catalase

In vitro: -

In vivo: mouse model of PD

1. Attenuate neuro inflammation and bigrostriatal degeneration

2. Prolong blood circulation time

3. Targeted diseased sites

4. Bioimaging

[123]

PD

BMMs

Polymer

Catalase

In vitro: -

In vivo: MPTP-treated mice

1. Reduce oxidative stress in animal models of PD

2. Release in active form for greater than 24 h

[124]

AD

Mouse peritoneal macrophages

Solid lipid

Genistein

In vitro: HT22

In vivo: mouse model of AD

1. Delivery functional antioxidant to neuronal mitochondria

2. Cross the BBB and selective target to neurons

[127]

Encephalitis

monocyte-macrophages

Magnetic nanoparticles

Catalase

In vitro: -

In vivo: LPS-induced brain inflammation

1. Target drug to the inflamed brain

2. Deactivate free radicals released by activating microglia

[167]

Glioma

RAW264.7

DSPE-PEG

IR-792

In vitro: U87L

In vivo: orthotopic glioblastoma model

1. Cross BBB and target to tumor site

2. Targeted tumor imaging

3. Combine with PTT and chemotherapy

[168]

Glioma

RAW264.7

MnO₂

Cisplatin

In vitro: C6 cells

In vivo: orthotopic glioblastoma model

1. Magnetic resonance imaging-guided chemotherapy/chemo-dynamic therapy

2. Good colloidal stability

3. Prolong blood circulation time

[169]

Glioma

Alveolar macrophages

Gold-silica

-

In vitro: C6 cells

In vivo: rat mouse model of C6 cells

1. PTT

2. Effective in vivo in preventing or delaying tumor development

[170]

Glioma

RAW264.7

Silica

DOX

In vitro: U87MG cells

In vivo: U87MG xenograft model

1. Minimally release drug molecules in the early hours of cell entry

2. High tumor accumulation

3. Efficient tumor growth suppression

[171]

Spinal cord injury

RAW264.7

Liposome

Minocycline

In vitro: inflamed HUVECs

In vivo: Spinal cord injury model

1. Actively targeted delivery

2. Decrease cellular uptake in RAW264.7 immune cells

3. Strengthen binding to damaged endothelial cells

4. A comprehensive therapeutic effect

[132]

RAW264.7

-

Nerve growth factor

In vitro: PC12

In vivo: oxidative

stress model of PC12 cells

1. Effectively cellular uptake by PC12 cells and suppression of neuronal apoptosis

2. Good targeting capacity

3. Good behavioral and histological recovery effects

[131]

Acute ischemic stroke

Primary macrophage

MnO₂

Fingolimod

In vitro: SH-SY5Y cells

In vivo: rat model of transient middle cerebral artery occlusion/reperfusion

1. Actively accumulation in the damaged brain

2. Promote the transition of M1 microglia to M2 microglia

3. Reverse the proinflammatory microenvironment and reinforce the survival of damaged neuron

4. Imaging

[133]

Immune disease

Rheumatoid arthritis

RAW264.7 derived exosomes

-

miRNA

In vitro: HEK-293 T cells and RAW 264.7

In vivo: collagen-induced arthritis model

1. Attenuate inflammation and angiogenesis

2. Inhibit the expression of HNF4A to activate the JAK/STAT3 signaling pathway

[136]

RAW264.7 derived exosomes

PLGA

-

In vitro: HUVECs

In vivo: collagen-induced arthritis model

1. Enhanced targeting effect in vivo in collagen-induced arthritis

2. Bind some RA-promoting cytokines

3. Good biocompatibility

[139]

KG-1 macrophages

Silicon

-

In vitro: EA.hy 926, HEK-293 and hEpG2

In vivo: -

1. Prolong circulation time

2. No activating of immune system

3. Attenuate the immune-stimulative potential of particles

[138]

RAW264.7 derived M2 exosomes

-

Plasmid DNA; betamethasone sodium phosphate

In vitro: RAW264.7

In vivo: collagen-induced arthritis model

1. Promote macrophage polarization

2. Good accumulation at inflamed joint sites

3. High anti-inflammatory activity

4. Non-toxic both in vitro and in vivo

[137]

RAW264.7

ZIF-8

Dexamethasone

In vitro: RAW264.7

In vivo: Collagen-induced arthritis model

1. High drug loading and encapsulation efficiency

2. High stability

3. Long circulation time

4. Sustained drug release in inflamed joint tissues

[65]

Peritoneal macrophages

PLGA

Dendrobium polysaccharides

In vitro: RAW264.7

In vivo: vaccinated mice and restimulated with ovalbumin

1. Promote antigen uptake by macrophage and lymphocyte proliferation

2. Increase the expression of MHC II, CD80 and CD86

3. Upregulate the ratio of CD4⁺ to CD8⁺ T cells in immunized mice

[172]

Others

Osteoarthritis

Alveolar macrophage cell

Gold

-

In vitro: cartilage explants

In vivo: -

1. Superior efficacy in sponging the pro-inflammatory cytokines

2. Alleviating OA inflammation and matrix degradation

3. Enhanced therapeutic efficiency

[144]

Allergic asthma

BMMs

PLGA

Dnmt3aos

In vitro: M2 macrophage

In vivo: allergic asthma mice

1. Ameliorate allergic asthma with a marked reduction of lung inflammation

2. Retain over 48 h and target m2 macrophages

3. No obvious immune function suppression of host

[143]

Ulcerative colitis

RAW264.7

βCyclodextrin

Rosiglitazone

In vitro: BMDM and Caco-2 cells

In vivo: dextran sulfate sodium salt -induced colitis mice model

1. Effectively polarized macrophage to M2

2. Protect epithelial cells from oxidative stress

3. High targeting efficiency

4. Significant therapeutic effects in vivo

[39]

RAW264.7

MOFs

Carbon nanodots and plasmid

In vitro: colon-26 cells and RAW 264.7

In vivo: dextran sulfate sodium salt-induced UC model

1. Scavenge ROS effectively

2. pH-responsive, immune escape, and inflammation targeting

3. Reduced the expression of proinflammatory cytokines

[141]

Kidney

RAW264.7 derived exosomes

-

Dexamethasone

In vitro: -

In vivo: LPS- or ADR-induced renal inflammation and fibrosis

1. Effectively delivered into inflamed kidney

2. Significant anti-inflammatory efficacy

3. Significantly attenuated renal injury

[140]

Acute pancreatitis

J774A.1

PLGA

-

In vitro: J774A.1 macrophages

In vivo: acute pancreatitis

mouse model

1. High biocompatibility

2. Effective protect against disease-associated inflammation, tissue damage and lethality

[142]